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Mai BHA. Seroprevalence of Bartonella quintana infection: A systematic review. J Glob Infect Dis 2022; 14:50-56. [PMID: 35910824 PMCID: PMC9336607 DOI: 10.4103/jgid.jgid_220_21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 11/20/2021] [Accepted: 12/24/2021] [Indexed: 11/23/2022] Open
Abstract
Introduction: Bartonella quintana is an anaerobic bacillus whose main target is the erythrocyte. This bacterium transmitted by the body louse notably infected the soldiers of the First World War from where the name of this disease: fever of the trenches. The 90s marked the return of this bacterial infection. B. quintana infection in the homeless was reported in the literature with a high incidence in these populations worldwide. This upsurge of cases justified this study for a better understanding of B. quintana infections. Methods: We conducted a systematic review to evaluate the seroprevalence of B. quintana infection by using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to collect scientific papers from PubMed and Google Scholar based on combining keywords. Results: The review included 45 articles published from April 1996 to March 2020 with 84 subpopulations of 21 countries from 4 continents; among them, 61 subpopulations had a positive rate from 0.2% to 65%. These subpopulations were divided into four main groups: homeless people, healthy people, blood donors, and symptoms/diseases. Homeless people were the main target of this infection, and three factors related to susceptibility were homeless period, age, and alcoholism. 6/11, 12/20, and 32/41 subpopulations of healthy people, blood donors, symptoms/diseases, respectively, had a positive percentage. However, factors of exposure in these three groups were not mentioned. Other reservoirs, vectors, and transmitted routes were identified to partially explain the worldwide spread of the infection, and it is important to have more further investigations to identify potential risk factors. This will help to limit contamination and prevent effectively. Conclusions: This serological overview indicated the importance of B. quintana infection that has emerged in multiple regions, touched worldwide populations.
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Jalili M, Nourmohammadi H, Sayehmiri K. Chlamydia pneumoniae and Mycoplasma pneumoniae as two Emerging Risk Factors in Atherosclerosis: Meta-Analysis Study and Systematic Review. Infect Disord Drug Targets 2021; 22:e210921196697. [PMID: 34548004 DOI: 10.2174/1871526521666210921121423] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 04/22/2021] [Accepted: 05/19/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Previous studies suggested an association between Chlamydia pneumoniae and Mycoplasma pneumonia with atherosclerosis, separately. Until now, according to inconsistent information, the relationship between C.pneumoniae and M.pneumoniae with atherosclerosis is controversial. OBJECTIVE the aim of this study, investigate of the association between C.pneumoniae and M.pneumoniae as two separate risk factors with atherosclerosis by systematic review and meta-analysis study. METHODS We searched databases such as Pubmed, SID, Magiran, Google scholar and Iranmedex using the following keywords in English and Persian language as C. pneumoniae , M. pneumoniae and atherosclerosis. Data were analyzed with meta-analysis and a random effect model. Also, in this study Heterogeneity of articles were estimated by using I2 index. Finally, data was analyzed with STAT (version 11.2) Results: Among thirty-eight articles for C. pneumoniae and five articles for M. pneumoniae individually reviewed that included 2980 samples for M. pneumoniae and 23298 samples for C. pneumoniae, result demonstrated that association between M. pneumoniae and C. pneumoniae with atherosclerosis is significant with OR (odd ratio) = 1.58 (95% Confidence Interval (CI): 1.00 to 2.50), OR (odd ratio) = 2.25(95% Confidence Interval (CI): 1.91 to 2.64), respectively. CONCLUSION This systematic review study provides strong evidence for the role of persistent bacterial infection such as M. pneumoniae and C. pneumoniae in potential atherosclerosis. Thus, a novel way should be employed for the complete management of bacterial infection.
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Affiliation(s)
- Mahsa Jalili
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan. Iran
| | - Hassan Nourmohammadi
- Department of Internal Medicine, School of Medicine, Shahid Mostafa Khomaeini Hospital, Ilam University of Medical sciences. Iran
| | - Kourosh Sayehmiri
- Psychosocial Injuries Research Center, Ilam University of Medical Sciences, Ilam. Iran
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3
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Chlamydia pneumoniae and chronic asthma: Updated systematic review and meta-analysis of population attributable risk. PLoS One 2021; 16:e0250034. [PMID: 33872336 PMCID: PMC8055030 DOI: 10.1371/journal.pone.0250034] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 03/24/2021] [Indexed: 12/02/2022] Open
Abstract
Background Chlamydia pneumoniae (Cp) is an obligate intracellular human respiratory pathogen producing persisting lung infection with a plausible link to asthma pathogenesis. The population attributable risk of potentially treatable Cp infection in asthma has not been reported. Methods The author searched from 2000 to 2020 inclusive for previously un-reviewed and new cross sectional and prospective controlled studies of Cp biomarkers and chronic asthma in both children and adults. Qualitative descriptive results and quantitative estimates of population attributable risk for selected biomarkers (specific IgG, IgA and IgE) are presented. Findings No large, long-term prospective population-based studies of Cp infection and asthma were identified. About half of case-control studies reported one or more significant associations of Cp biomarkers and chronic asthma. Heterogeneity of results by age group (pediatric v adult asthma), severity category (severe/uncontrolled, moderate/partly controlled, mild/controlled) and antibody isotype (specific IgG, IgA, IgE) were suggested by the qualitative results and confirmed by meta-analyses. The population attributable risks for Cp-specific IgG and IgA were nul in children and were 6% (95% confidence interval 2%-10%, p = 0.002) and 13% (9%-18%, p<0.00001) respectively in adults. In contrast to the nul or small population attributable risks for Cp-specific IgG and IgA, the population attributable risk for C. pneumoniae-specific IgE (children and adults combined) was 47% (39%-55%, p<0.00001). In the subset of studies that reported on asthma severity categories, Cp biomarkers were positively and significantly (P<0.00001) associated with asthma severity. Interpretation C. pneumoniae-specific IgE is strongly associated with asthma and asthma severity, suggesting a possible mechanism linking chronic Cp infection with asthma in a subset of individuals with asthma. Infection biomarkers should be included in future macrolide treatment trials for severe and uncontrolled asthma.
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The global prevalence of Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus and Herpes simplex virus in patients with coronary artery disease: A systematic review and meta-analysis. Microb Pathog 2020; 152:104572. [PMID: 33166619 DOI: 10.1016/j.micpath.2020.104572] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 09/29/2020] [Accepted: 10/14/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Coronary Artery Disease (CAD) is one of the most important causes of death worldwide. The aim of this study was to determine the prevalence of C. pneumoniae, H. pylori, Cytomegalovirus (CMV) and Herpes simplex virus (HSV) in CAD patients based on published serological and molecular studies. METHODS A systematic literature search was conducted in Medline (via PubMed), Embase, Scopus and Web of Science databases (1996-2019). Both molecular and serological studies were analyzed using STATA software (Version 14). RESULTS 145 studies were included for final analysis. We gathered and investigated the prevalence of C. pneumoniae (25.1% [95% confidence interval (CI) 21.5-28.8%]), H. pylori (12.8% [(95% CI) 4.0-22.0%]), CMV (64.4% [(95% CI) 57.7-73.0%]) and HSV (31.8% [(95% CI) 21.5-42.2%]) in CAD patients from the analysis of molecular studies. Additionally, in serological studies, the prevalence of mentioned pathogens were 72.7% [(95% CI) 67.8-77.6%], 63.3% [(95% CI) 60.0-66.5%], 62.2% [(95% CI) 58.0-66.3%] and 34.3% [(95% CI) 23.6-45.1%] respectively. CONCLUSION Interestingly, there was only a significant increase in the prevalence of C. pneumoniae and H. pylori in serological studies compared to the reported data from molecular studies, while the prevalence of CMV and HSV were the same in both types of studies.
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Iliescu EA, Fiebig MF, Morton AR, Sankar–Mistry P. Chlamydia PneumoniaeDNA in Peripheral Blood Mononuclear Cells in Peritoneal Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686080002000624] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
ObjectiveThe aim of the present study was to examine the association between infection with Chlamydia pneumoniae and symptomatic atherosclerosis in peritoneal dialysis (PD) patients.DesignCross-sectional study.SettingPeritoneal Dialysis Unit of Kingston General Hospital.PatientsFifty-five prevalent PD patients.Outcome Measures( 1 ) Infection with C. pneumoniae diagnosed by detection of DNA in peripheral blood mono-nuclear cells (PBMCs) using polymerase chain reaction. ( 2 ) Symptomatic atherosclerosis involving the coronary, cerebral, or peripheral circulation.ResultsThe DNA of C. pneumoniae was detected in PBMCs in 33 patients (60.0%). Atherosclerosis was present in 16 of 33 (48%) PBMC C. pneumoniae DNA–positive patients, and in 10 of 22 (45%) PBMC C. pneumoniae DNA–negative patients ( p = 0.83). Using multiple logistic regression and controlling for a number of known cardiovascular risk factors, PBMC C. pneumoniae DNA status was not predictive of atherosclerosis. The only significant independent predictors of atherosclerosis were diabetes and age.ConclusionsIn prevalent PD patients, a high prevalence of symptomatic atherosclerosis and of Chlamydia pneumoniae DNA in PBMCs were seen; however, the results of the present study do not support the presence of an association between infection with C. pneumoniae and atherosclerosis.
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Affiliation(s)
| | | | | | - Perin Sankar–Mistry
- Department of Microbiology and Immunology, Queen's University
- Public Health Laboratory, Ministry of Health, Kingston, Ontario, Canada
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Fox M, Knorr DA, Haptonstall KM. Alzheimer's disease and symbiotic microbiota: an evolutionary medicine perspective. Ann N Y Acad Sci 2019; 1449:3-24. [PMID: 31180143 DOI: 10.1111/nyas.14129] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 04/19/2019] [Accepted: 05/03/2019] [Indexed: 12/15/2022]
Abstract
Microorganisms resident in our bodies participate in a variety of regulatory and pathogenic processes. Here, we describe how etiological pathways implicated in Alzheimer's disease (AD) may be regulated or disturbed by symbiotic microbial activity. Furthermore, the composition of symbiotic microbes has changed dramatically across human history alongside the rise of agriculturalism, industrialization, and globalization. We postulate that each of these lifestyle transitions engendered progressive depletion of microbial diversity and enhancement of virulence, thereby enhancing AD risk pathways. It is likely that the human life span extended into the eighth decade tens of thousands of years ago, yet little is known about premodern geriatric epidemiology. We propose that microbiota of the gut, oral cavity, nasal cavity, and brain may modulate AD pathogenesis, and that changes in the microbial composition of these body regions across history suggest escalation of AD risk. Dysbiosis may promote immunoregulatory dysfunction due to inadequate education of the immune system, chronic inflammation, and epithelial barrier permeability. Subsequently, proinflammatory agents-and occasionally microbes-may infiltrate the brain and promote AD pathogenic processes. APOE genotypes appear to moderate the effect of dysbiosis on AD risk. Elucidating the effect of symbiotic microbiota on AD pathogenesis could contribute to basic and translational research.
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Affiliation(s)
- Molly Fox
- Department of Anthropology, University of California Los Angeles, Los Angeles, California.,Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California
| | - Delaney A Knorr
- Department of Anthropology, University of California Los Angeles, Los Angeles, California
| | - Kacey M Haptonstall
- Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, California
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Sessa R, Pietro MDI, Schiavoni G, Galdiero M, Cipriani P, Romano S, Zagaglia C, Santino I, Faccilongo S, Piano MD. Chlamydia Pneumoniae in Asymptomatic Carotid Atherosclerosis. Int J Immunopathol Pharmacol 2018. [DOI: 10.1177/205873920601900111] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We evaluated, in 415 patients with asymptomatic carotid atherosclerosis: (i) the prevalence of C. pneumoniae DNA in atherosclerotic carotid plaques and peripheral blood mononuclear cells (PBMC); (ii) the distribution of C. pneumoniae in atherosclerotic carotid plaques and PBMC from the same patients; (iii) the correlation between circulating anti-chlamydial antibodies and the presence of C. pneumoniae DNA. Overall, 160 atherosclerotic carotid plaques and 174 PBMC specimens from patients with asymptomatic carotid atherosclerosis were examined by ompA nested touchdown PCR for presence of C. pneumoniae. In addition, C. pneumoniae DNA was detected in 81 specimens of atherosclerotic carotid plaque and PBMC obtained from the same patients. C. pneumoniae DNA was found in 36.9% of atherosclerotic carotid plaques and in 40.2% of PBMC specimens examined (P=NS). With regard to 81 patients, C. pneumoniae DNA was detected in 27.2% of atherosclerotic carotid plaques and in 44.4% of PBMC specimens (P=0.05). In 18 patients, the presence of C. pneumoniae DNA in PBMC specimens and atherosclerotic carotid plaques coincided (P=0.005). No statistically significant association was found between anti-C pneumoniae antibodies (IgG and IgA) and positive PCR results. In conclusion, our results suggest that the detection of C. pneumoniae DNA in PBMC specimens seems to be a first-choice method to identify the patients at risk for endovascular chlamydial infection.
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Affiliation(s)
- R. Sessa
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. DI Pietro
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - G. Schiavoni
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. Galdiero
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
| | - P. Cipriani
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - S. Romano
- Department of Internal Medicine, Cardiology, University of L'Aquila, Italy
| | - C. Zagaglia
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - I. Santino
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - S. Faccilongo
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. Del Piano
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
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Zigangirova NA, Morgunova EY, Fedina ED, Shevyagina NV, Borovaya TG, Zhukhovitsky VG, Kyle NH, Petyaev IM. Lycopene Inhibits Propagation of Chlamydia Infection. SCIENTIFICA 2017; 2017:1478625. [PMID: 28948060 PMCID: PMC5602621 DOI: 10.1155/2017/1478625] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 06/11/2017] [Indexed: 06/07/2023]
Abstract
Chlamydiaceae is a family of obligate intracellular pathogenic bacteria with similar developmental cycles and cell biology responsible for a wide range of diseases in different hosts including genital and eye inflammatory diseases, arthritis, and inflammatory diseases of the respiratory and cardiovascular systems. In the present paper, we report that lycopene, one of the main dietary carotenoids, which is present in tomato and some other fruits, has a strong inhibitory effect on C. trachomatis and C. pneumoniae infections in alveolar macrophages. This finding was documented by both immunofluorescence analysis and electron microscopy. It was noted that lycopene treatment inhibited intracellular phase of the chlamydial developmental cycle and resulted in a significant loss of infectious progeny. The antichlamydial effect of lycopene was also confirmed in a clinical setting. There was a significant reduction of IgG antibodies against C. pneumoniae in the serum of volunteers treated for a month with oral ingestion of 7 mg of lycopene. Additional studies are needed to further explore the antichlamydial activity of lycopene and its possible effect on C. pneumoniae in relation to antichlamydial activity of lycopene to mechanisms of atherosclerosis.
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Affiliation(s)
- Naylia A. Zigangirova
- Gamaleya Center of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia
| | - Elena Y. Morgunova
- Gamaleya Center of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia
| | - Elena D. Fedina
- Gamaleya Center of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia
| | - Natalia V. Shevyagina
- Gamaleya Center of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia
| | - Tatiana G. Borovaya
- Gamaleya Center of Epidemiology and Microbiology, Ministry of Health, Moscow, Russia
| | | | - Nigel H. Kyle
- Lycotec Ltd., Granta Park Campus, Cambridge CB21 6GP, UK
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9
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Kalayci F, Ozdemir A, Saribas S, Yuksel P, Ergin S, Kuskucu AM, Poyraz CA, Balcioglu I, Alpay N, Kurt A, Sezgin Z, Kocak BT, Icel RS, Can G, Tokman HB, Kocazeybek B. The relationship of Chlamydophila pneumoniae with schizophrenia: The role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in this relationship. Rev Argent Microbiol 2017; 49:39-49. [PMID: 28256360 DOI: 10.1016/j.ram.2016.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 09/06/2016] [Accepted: 09/12/2016] [Indexed: 10/20/2022] Open
Abstract
Several pathogens have been suspected of playing a role in the pathogenesis of schizophrenia. Chronic inflammation has been proposed to occur as a result of persistent infection caused by Chlamydophila pneumoniae cells that reside in brain endothelial cells for many years. It was recently hypothesized that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) may play prominent roles in the development of schizophrenia. NT-3 and BDNF levels have been suggested to change in response to various manifestations of infection. Therefore, we aimed to elucidate the roles of BDNF and NT3 in the schizophrenia-C. pneumoniae infection relationship. RT-PCR, immunofluorescence and ELISA methods were used. Fifty patients suffering from schizophrenia and 35 healthy individuals were included as the patient group (PG) and the healthy control group (HCG), respectively. We detected persistent infection in 14 of the 50 individuals in the PG and in 1 of the 35 individuals in the HCG. A significant difference was found between the two groups (p<0.05). Twenty-two individuals in the PG and 13 in the HCG showed seropositivity for past C. pneumoniae infection, and no difference was observed between the groups (p>0.05). C. pneumoniae DNA was not detected in any group. A significant difference in NT-3 levels was observed between the groups, with very low levels in the PG (p<0.001). A significant difference in BDNF levels was also found, with lower levels in the PG (p<0.05). The mean serum NT-3 level was higher in the PG cases with C. pneumoniae seropositivity than in seronegative cases; however, this difference was not statistically significant (p>0.05). In conclusion, we suggest that NT-3 levels during persistent C. pneumoniae infection may play a role in this relationship.
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Affiliation(s)
- Fatma Kalayci
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Armagan Ozdemir
- T.C. Health Ministry Bakirkoy Mental Health and Neurology Training and Research Hospital Psychiatry Clinic, Istanbul, Turkey
| | - Suat Saribas
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Pelin Yuksel
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Sevgi Ergin
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Ali Mert Kuskucu
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Cana Aksoy Poyraz
- Istanbul University, Cerrahpasa Medical Faculty, Department of Psychiatry, Istanbul, Turkey
| | - Ibrahim Balcioglu
- Istanbul University, Cerrahpasa Medical Faculty, Department of Psychiatry, Istanbul, Turkey
| | - Nihat Alpay
- T.C. Health Ministry Bakirkoy Mental Health and Neurology Training and Research Hospital Psychiatry Clinic, Istanbul, Turkey
| | - Aykut Kurt
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Zeynep Sezgin
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Biochemistry, Istanbul, Turkey
| | - Banu Tufan Kocak
- T.C. Health Ministry Erenkoy Mental Health and Neurology Training and Research Hospital, Istanbul, Turkey
| | - Rana Sucu Icel
- T.C. Health Ministry, Sisli Etfal Education and Research Hospital, Department of Blood Center, Istanbul, Turkey
| | - Gunay Can
- Istanbul University, Cerrahpasa Medical Faculty, Department of Public Health, Istanbul, Turkey
| | - Hrisi Bahar Tokman
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Bekir Kocazeybek
- Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey.
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10
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Sessa R, Schiavoni G, Di Pietro M, Petrucca A, Cipriani P, Puopolo M, Zagaglia C, Fallucca S, Del Piano M. Chlamydia Pneumoniae in PBMC: Reproducibility of the OMPA Nested Touchdown PCR. Int J Immunopathol Pharmacol 2016; 18:113-20. [PMID: 15698516 DOI: 10.1177/039463200501800112] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The aim of our study was to evaluate whether the replicate PCR testing may provide more accurate estimates of C. pneumoniae DNA prevalence in PBMC of patients undergoing carotid endarterectomy. Clinical sensitivity and reproducibility of ompA nested touchdown PCR was also performed. Clinical sensitivity and reproducibility was examined by testing C. pneumoniae-negative PBMC spiked with serial dilutions of semipurified C. pneumoniae elementary bodies (from 8 to 0.002 IFU/ml). Detection of C. pneumoniae DNA was performed by ompA nested touchdown PCR. Each clinical and spiked PBMC DNA specimen was analyzed in replicates of 1,3,5 and 10. PCR results of serial dilutions of C. pneumoniae DNA performed in replicates of 10 were analysed by probit analysis. C. pneumoniae DNA was detected in 14 of the 30 (46.7%) PBMC clinical specimens examined when 10 replicates were tested. When we analyzed 1, 3 and 5 replicates, 4 (13.3%), 7(23.3%), 12(40%) of the 30 specimens were positive, respectively. The limit of detection of ompA nested PCR touchdown was 0.008 IFU/ml when 10 replicates were tested. The ompA nested PCR had reproducibility scores of 10 for 10 from 8 to 4 IFU/ml concentration, but scores decreased for smaller numbers of IFU/ml. Our results showed that repeat testing of the same specimen increased clinical sensitivity as well as reproducibility of the ompA nested touchdown PCR. In conclusion the replicate PCR testing improves the performance of ompA nested touchdown PCR and provides a more accurate estimates of the prevalence of C. pneumoniae in PBMC of patients with atherosclerotic cardiovascular disease.
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Affiliation(s)
- R Sessa
- Department of Public Health Sciences, "La Sapienza" University, Rome, Italy.
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11
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Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci. Sci Rep 2016; 6:19058. [PMID: 26785849 PMCID: PMC4726309 DOI: 10.1038/srep19058] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 12/02/2015] [Indexed: 01/03/2023] Open
Abstract
Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.
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12
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Herweg JA, Rudel T. Interaction of Chlamydiae with human macrophages. FEBS J 2015; 283:608-18. [PMID: 26613554 DOI: 10.1111/febs.13609] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 11/13/2015] [Accepted: 11/24/2015] [Indexed: 11/28/2022]
Abstract
The phylum Chlamydiae contains several members that are well-known human pathogens, like Chlamydia trachomatis and C. pneumoniae. Establishing a chronic bacterial infection requires the active evasion of the host immune response. A major arm of the innate immune defence is constituted by macrophages, which fight infections by removing bacteria and triggering an adaptive immune response. However, some pathogenic Chlamydia infect and survive in macrophages at least for a certain period of time. Therefore, macrophages can serve as vehicles for the dissemination of bacterial infections from the primary infection site via the urogenital or respiratory tract to distant sites in the body. The capacity to infect macrophages seems to depend on the chlamydial strain and the source of macrophages. In vitro infections of macrophages with C. trachomatis, C. psittaci and C. pneumoniae reveal low efficiency of infection and progeny formation, as well as failure to develop mature inclusions. In contrast, the emerging pathogen, Simkania negevensis, actively replicates in macrophages. Here we summarize the current knowledge of the intracellular and molecular key mechanisms of C. trachomatis, C. pneumoniae and S. negevensis infections in human macrophages.
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Affiliation(s)
- Jo-Ana Herweg
- Biocenter, Department of Microbiology, University of Würzburg, Germany
| | - Thomas Rudel
- Biocenter, Department of Microbiology, University of Würzburg, Germany
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13
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Cheeniyil A, Evani SJ, Dallo SF, Ramasubramanian AK. Shear stress upregulates IL-1β secretion by Chlamydia pneumoniae- infected monocytes. Biotechnol Bioeng 2015; 112:838-42. [PMID: 25336058 DOI: 10.1002/bit.25486] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Revised: 09/19/2014] [Accepted: 10/13/2014] [Indexed: 12/13/2022]
Abstract
Infectious agents are increasingly implicated in the development and progression of chronic inflammatory diseases. Several lines of evidence suggest that the common intracellular respiratory pathogen, Chlamydia pneumoniae contributes to the well-established risk factors of atherosclerosis but the exact mechanism is not well understood. It is believed that C. pneumoniae-infected monocytes travel from the lung to the atherosclerotic foci, during which the cells experience mechanical stimuli due to blood flow. In this work, we characterized the effect of physiological levels of shear stress on C. pneumoniae-infected human monocytes in an in vitro flow model. We found that a shear stress of 5 dyn/cm(2) enhanced the expression of pro-inflammatory cytokine IL-1β only in infected, but not in uninfected, monocytes. We also found that this enhancement is due to the upregulation of IL-1β gene expression due to shear stress. Our results demonstrate that mechanotransduction is an important, heretofore unaddressed, determinant of inflammatory response to an infection.
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Affiliation(s)
- Aswathi Cheeniyil
- Department of Biomedical Engineering, and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, 78249.
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14
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Lim C, Hammond CJ, Hingley ST, Balin BJ. Chlamydia pneumoniae infection of monocytes in vitro stimulates innate and adaptive immune responses relevant to those in Alzheimer's disease. J Neuroinflammation 2014; 11:217. [PMID: 25540075 PMCID: PMC4295513 DOI: 10.1186/s12974-014-0217-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Accepted: 12/07/2014] [Indexed: 11/24/2022] Open
Abstract
Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which infection with Chlamydia pneumoniae (Cpn) has been associated. Cpn is an obligate intracellular respiratory pathogen that may enter the central nervous system (CNS) following infection and trafficking of monocytes through the blood-brain barrier. Following this entry, these cells may secrete pro-inflammatory cytokines and chemokines that have been identified in the AD brain, which have been thought to contribute to AD neurodegeneration. The objectives of this work were: (i) to determine if Cpn infection influences monocyte gene transcript expression at 48 hours post-infection and (ii) to analyze whether pro-inflammatory cytokines are produced and secreted from these cells over 24 to 120 hours post-infection. Methods Gene transcription was analyzed by RT-PCR using an innate and adaptive immunity microarray with 84 genes organized into 5 functional categories: inflammatory response, host defense against bacteria, antibacterial humoral response, septic shock, and cytokines, chemokines and their receptors. Statistical analysis of the results was performed using the Student's t-test. P-values ≤ 0.05 were considered to be significant. ELISA was performed on supernatants from uninfected and Cpn-infected THP1 monocytes followed by statistical analysis with ANOVA. Results When Cpn-infected THP1 human monocytes were compared to control uninfected monocytes at 48 hours post-infection, 17 genes were found to have a significant 4-fold or greater expression, and no gene expression was found to be down-regulated. Furthermore, cytokine secretion (IL-1β, IL-6, IL-8) appears to be maintained for an extended period of infection. Conclusions Utilizing RT-PCR and ELISA techniques, our data demonstrate that Cpn infection of THP1 human monocytes promotes an innate immune response and suggests a potential role in the initiation of inflammation in sporadic/late-onset Alzheimer’s disease.
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Affiliation(s)
- Charles Lim
- Department of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA, 19131, USA.
| | - Christine J Hammond
- Department of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA, 19131, USA.
| | - Susan T Hingley
- Department of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA, 19131, USA.
| | - Brian J Balin
- Department of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA, 19131, USA.
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15
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Abstract
We compared five different polymerase chain reaction (PCR) assays for the detection of Chlamydophila pneumoniae DNA using highly purified elementary bodies (EBs) and peripheral blood mononuclear cells (PBMCs) from healthy blood donors. The primers were as follows; two targeting the 16S rRNA gene, one targeting the ompA gene, one targeting the Pst-I gene, and one targeting the 53 kDa outer membrane protein gene. The 16S rRNA touchdown enzyme time release (TETR) PCR, the ompA nested PCR and the 53 kDa nested PCR were the most sensitive assays and could detect one or more EB per assay. These three PCRs also had the same reproducibility, but the minimal amount of C. pneumoniae that could be reproducibly detected (10 of 10 testing positive) was 20 EBs. In a sample of specimens from healthy blood donors, we found 5 of 77 (6.5%) PBMCs specimens to have C. pneumoniae DNA according to the nested ompA PCR. Specimens with the 16S rRNA TETR and 53 kDa nested assays were found to have C. pneumoniae DNA 7 of 77 (9.1%) and 18 of 77 (23.4%) specimens, respectively. The other two assays failed to detect even a single positive. However, the detection rate decreased with repeated testing of the same samples. Our newly designed 53 kDa nested PCR may be as useful as the other four recommended PCR assays and may be a more useful assay for the detection of C. pneumoniae DNA from PBMCs.
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Affiliation(s)
- Hiroshi Fukano
- Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
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16
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Di Pietro M, Filardo S, De Santis F, Sessa R. Chlamydia pneumoniae infection in atherosclerotic lesion development through oxidative stress: a brief overview. Int J Mol Sci 2013; 14:15105-20. [PMID: 23877837 PMCID: PMC3742290 DOI: 10.3390/ijms140715105] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Revised: 07/04/2013] [Accepted: 07/10/2013] [Indexed: 12/11/2022] Open
Abstract
Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development.
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Affiliation(s)
- Marisa Di Pietro
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
| | - Simone Filardo
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
| | - Fiorenzo De Santis
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
| | - Rosa Sessa
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
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17
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Atherosclerosis Induced by Chlamydophila pneumoniae: A Controversial Theory. Interdiscip Perspect Infect Dis 2013; 2013:941392. [PMID: 23956742 PMCID: PMC3730386 DOI: 10.1155/2013/941392] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 06/18/2013] [Indexed: 02/02/2023] Open
Abstract
More than a century ago, inflammation and infection were considered to have atherogenic effects. The old idea that coronary heart disease (CHD) possibly has an infectious etiology has only reemerged in recent years. Atherosclerosis is the main pathological process involved in CHD and is, logically, the first place to look for infectious etiology. The process of atherosclerosis itself provides the first hints of potential infectious cause. Smooth muscle proliferation, with subsequent intimal thickening, luminal narrowing, and endothelial degeneration, constitutes the natural history of atherosclerosis, being with the severity and speed of these changes. Both viral and bacterial pathogens have been proposed to be associated with the inflammatory changes found in atherosclerosis. Recently, Chlamydophila pneumoniae (C. pneumoniae) has been implicated as a possible etiologic agent of coronary artery disease and atherosclerosis. New evidence which supports a role for C. pneumoniae in the pathogenesis of atherosclerosis has emerged. C. pneumoniae has been detected in atherosclerotic arteries by several techniques, and the organism has been isolated from both coronary and carotid atheromas. Recent animal models have suggested that C. pneumoniae is capable of inducing atherosclerosis in both rabbit and mouse models of atherosclerosis. Furthermore, human clinical treatment studies which examined the use of antichlamydial macrolide antibiotics in patients with coronary atherosclerosis have been carried out. The causal relationship has not yet been proven, but ongoing large intervention trials and research on pathogenetic mechanisms may lead to the use of antimicrobial agents in the treatment of CHD in the future.
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18
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Joshi R, Khandelwal B, Joshi D, Gupta OP. Chlamydophila pneumoniae infection and cardiovascular disease. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2013; 5:169-81. [PMID: 23626952 PMCID: PMC3632020 DOI: 10.4103/1947-2714.109178] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Atherosclerosis is a multifactorial vascular inflammatory process; however, the inciting cause for inflammation remains unclear. Two decades ago, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae) infection was proposed as a putative etiologic agent. We performed a PubMed search using the keywords Chlamydia and atherosclerosis in a Boolean query to identify published studies on C. pneumoniae and its role in atherogenesis, and to understand research interest in this topic. We found 1,652 published articles on this topic between 1991 and 2011. We analyzed relevant published studies and found various serological, molecular, and animal modeling studies in the early period. Encouraged by positive results from these studies, more than a dozen antibiotic clinical-trials were subsequently conducted, which did not find clinical benefits of anti-Chlamydophila drug therapy. While many researchers believe that the organism is still important, negative clinical trials had a similar impact on overall research interest. With many novel mechanisms identified for atherogenesis, there is a need for newer paradigms in Chlamydophila-atherosclerosis research.
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Affiliation(s)
- Rajnish Joshi
- Department of Medicine, Sikkim Manipal Institute of Medical Sciences, Gangtok, India
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19
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García-Elorriaga G, Rey-Pineda GD. Human immunodeficiency virus, atherosclerosis and Chlamydophila pneumoniae. World J Clin Infect Dis 2012; 2:54-62. [DOI: 10.5495/wjcid.v2.i4.54] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Chlamydophila pneumoniae (C. pneumoniae) is an obligate, intracellular bacterium associated with a wide variety of acute and chronic diseases. C. pneumoniae infection is characterized by persistence and immunopathological damage to host target tissues, including the lung. Over the past 20 years, a variety of studies have investigated a possible link between C. pneumoniae infection and atherosclerosis, because of its role in all stages of atherosclerosis, from initial inflammatory lesions to plaque rupture. In the current highly active antiretroviral therapy (HAART) era, many human immunodeficiency virus (HIV)-infected patients are experiencing health problems that accompany the aging process, mainly the risk of cardiovascular disease (CVD). There is renewed interest in a link between atherosclerotic CVD and as yet poorly defined environmental exposures, including infectious agents. On the one hand, the patient with HIV and lipodystrophy caused by HAART and exacerbated by C. pneumoniae infection could be a factor of risk for atherosclerosis. An assessment of the therapy against C. pneumoniae and HAART should always be conducted. It is advisable that HIV-acquired immune deficiency syndrome patients undergo a serological test to determine exposure to C. pneumoniae and to assess treatment options. On the other hand, in patients with a positive serology to C. pneumoniae, an increment of the body mass index has been found; therefore, it is probable that the recurrent infection may play an important role in creating adverse endothelial conditions allowing the infection by C. pneumoniae in its chronic form, to damage the endothelial surface. Vascular studies would be necessary for corroboration.
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20
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Mannonen L, Markkula E, Puolakkainen M. Analysis of Chlamydia pneumoniae infection in mononuclear cells by reverse transcription-PCR targeted to chlamydial gene transcripts. Med Microbiol Immunol 2011; 200:143-54. [PMID: 21279651 DOI: 10.1007/s00430-011-0184-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2010] [Indexed: 01/12/2023]
Abstract
Chlamydia pneumoniae (C. pneumoniae) is an important etiological agent of respiratory infections including pneumonia. C. pneumoniae DNA can be detected in peripheral blood mononuclear cells indicating that monocytes can assist the spread of infection to other anatomical sites. Persistent infection established at these sites could promote inflammation and enhance pathology. Thus, the mononuclear cells are in a strategic position in the development of persistent infection. To investigate the intracellular replication and fate of C. pneumoniae in mononuclear cells, we have established an in vitro model in the human Mono Mac 6 cell line. In the present study, we analyzed the transcription of 11 C. pneumoniae genes in Mono Mac 6 cells during infection by real-time RT-PCR. Our results suggest that the transcriptional profile of the studied genes in monocytes is different from that seen in epithelial cells. Furthermore, our study shows that genes related to secretion are transcribed, and secreted bacterial proteins are also translated during infection of monocytes, creating novel opportunities for the management of chlamydial infection of monocytes.
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Affiliation(s)
- Laura Mannonen
- Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland.
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21
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Wang CM, Kaltenboeck B. Exacerbation of chronic inflammatory diseases by infectious agents: Fact or fiction? World J Diabetes 2010; 1:27-35. [PMID: 21537425 PMCID: PMC3083881 DOI: 10.4239/wjd.v1.i2.27] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2009] [Revised: 03/27/2010] [Accepted: 04/03/2010] [Indexed: 02/05/2023] Open
Abstract
Chronic inflammatory diseases caused by obesity represent critical public health concerns worldwide. In these diseases such as metabolic syndrome, diabetes and atherosclerosis, adipose tissue acts as an endocrine organ that releases large quantities of inflammatory mediators into circulation. Besides classically recognized effectors on the development of obesity and resultant conditions, infection has attracted attention as an enhancer of chronic inflammatory diseases. Infectious diseases have long been associated with obesity, metabolic syndrome, diabetes and atherosclerosis. However, the infectious hypothesis for chronic inflammatory diseases has been challenged by inconclusive clinical trials. Nevertheless, the large body of evidence accumulated over decades on the association of infectious diseases with obesity, diabetes and cardiovascular disease should not be disregarded. Instead, re-formulation of hypotheses of the mechanisms by which microbes affect obesity-associated diseases may be required with an emphasis on the early events in the progression of such diseases and the multifactorial nature of pathogen-host interactions. This review focuses on pathogens that directly promote obesity and on pathogens that cause chronic infections and thereby enhance metabolic diseases in obese patients. A new perspective on the interaction between infections and obesity-related diseases may improve management of chronic inflammatory diseases that rank high among global threats to human health.
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Affiliation(s)
- Cheng-Ming Wang
- Cheng-Ming Wang, Ross University School of Veterinary Medicine, PO Box 334, Basseterre, St. Kitts, West Indies
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22
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Karimi G, Samiei S, Hatami H, Gharehbaghian A, Vafaiyan V, Namini MT. Detection of Chlamydia pneumoniae in peripheral blood mononuclear cells of healthy blood donors in Tehran Regional Educational Blood Transfusion Centre. Transfus Med 2010; 20:237-43. [DOI: 10.1111/j.1365-3148.2010.01003.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Chlamydophila pneumoniae Infection and Its Role in Neurological Disorders. Interdiscip Perspect Infect Dis 2010; 2010:273573. [PMID: 20182626 PMCID: PMC2825657 DOI: 10.1155/2010/273573] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2009] [Accepted: 11/25/2009] [Indexed: 12/26/2022] Open
Abstract
Chlamydophila pneumoniae is an intracellular pathogen responsible for a number of different acute and chronic infections. The recent deepening of knowledge on the biology and the use of increasingly more sensitive and
specific molecular techniques has allowed demonstration of C. pneumoniae in
a large number of persons suffering from different diseases including cardiovascular (atherosclerosis and stroke) and central nervous system (CNS) disorders. Despite this, many important issues remain unanswered with regard to the role that C. pneumoniae may play in initiating atheroma or in the progression of the disease. A growing body of evidence concerns the involvement of this pathogen in chronic neurological disorders and particularly in Alzheimer's disease (AD) and Multiple Sclerosis (MS). Monocytes may traffic C. pneumoniae across the blood-brain-barrier, shed the organism in the
CNS and induce neuroinflammation. The demonstration of C. pneumoniae by
histopathological, molecular and culture techniques in the late-onset AD dementia has suggested a relationship between CNS infection with C. pneumoniae and the AD neuropathogenesis. In particular subsets of MS patients, C. pneumoniae could induce a chronic persistent brain infection acting as a cofactor in the development of the disease. The role of Chlamydia in the pathogenesis of mental or neurobehavioral disorders including schizophrenia and autism is uncertain and fragmentary and will require further
confirmation.
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24
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Saikku PAI. Chlamydia. Infect Dis (Lond) 2010. [DOI: 10.1016/b978-0-323-04579-7.00177-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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25
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Zou S, Wu Y, Cable R, Dorsey K, Tang Y, Hapip CA, Melmed R, Trouern-Trend J, Carrano D, Champion M, Fujii K, Fang C, Dodd R. A prospective study of multiple donor exposure blood recipients: surveillance value and limitations for hemovigilance. Transfusion 2010; 50:128-38. [DOI: 10.1111/j.1537-2995.2009.02386.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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26
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Palikhe A, Tiirola T, Puolakkainen M, Nieminen MS, Saikku P, Leinonen M, Sinisalo J. Chlamydia pneumoniae DNA is present in peripheral blood mononuclear cells during acute coronary syndrome and correlates with chlamydial lipopolysaccharide levels in serum. ACTA ACUST UNITED AC 2009; 41:201-5. [DOI: 10.1080/00365540902737968] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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27
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Rupp J, Pfleiderer L, Jugert C, Moeller S, Klinger M, Dalhoff K, Solbach W, Stenger S, Laskay T, van Zandbergen G. Chlamydia pneumoniae hides inside apoptotic neutrophils to silently infect and propagate in macrophages. PLoS One 2009; 4:e6020. [PMID: 19547701 PMCID: PMC2695784 DOI: 10.1371/journal.pone.0006020] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2009] [Accepted: 05/19/2009] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia) and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN) are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae. METHODOLOGY/PRINCIPAL FINDINGS We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ss production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-alpha response. CONCLUSIONS/SIGNIFICANCE Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host.
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Affiliation(s)
- Jan Rupp
- Institute of Medical Microbiology and Hygiene, University of Luebeck, Luebeck, Germany
- Medical Clinic III, University hospital Schleswig-Holstein, Luebeck, Germany
- * E-mail: (JR); (GvZ)
| | - Lisa Pfleiderer
- Institute of Medical Microbiology and Hygiene, University Clinic of Ulm, Ulm, Germany
| | - Christiane Jugert
- Institute of Medical Microbiology and Hygiene, University of Luebeck, Luebeck, Germany
| | - Sonja Moeller
- Institute of Medical Microbiology and Hygiene, University of Luebeck, Luebeck, Germany
| | | | - Klaus Dalhoff
- Medical Clinic III, University hospital Schleswig-Holstein, Luebeck, Germany
| | - Werner Solbach
- Institute of Medical Microbiology and Hygiene, University of Luebeck, Luebeck, Germany
| | - Steffen Stenger
- Institute of Medical Microbiology and Hygiene, University Clinic of Ulm, Ulm, Germany
| | - Tamas Laskay
- Institute of Medical Microbiology and Hygiene, University of Luebeck, Luebeck, Germany
| | - Ger van Zandbergen
- Institute of Medical Microbiology and Hygiene, University Clinic of Ulm, Ulm, Germany
- * E-mail: (JR); (GvZ)
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28
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Gomez LM, Parry S. Trophoblast infection with Chlamydia pneumoniae and adverse pregnancy outcomes associated with placental dysfunction. Am J Obstet Gynecol 2009; 200:526.e1-7. [PMID: 19375572 DOI: 10.1016/j.ajog.2009.03.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2008] [Revised: 01/30/2009] [Accepted: 03/06/2009] [Indexed: 10/20/2022]
Abstract
OBJECTIVE We sought to determine whether Chlamydia pneumoniae impairs invasive trophoblast function and is associated with preeclampsia. STUDY DESIGN We conducted cell viability and invasion assays using primary extravillous trophoblast cells isolated from first-trimester placentas. We performed a case-control study to identify C pneumoniae in trophoblast cells dissected by laser capture microscopy from placentas in women with severe preeclampsia and control subjects who delivered at term. RESULTS Trophoblast cell viability and invasion through extracellular matrices were decreased after infection with C pneumoniae (both P < .05). C pneumoniae DNA was detected in trophoblast cells in 15/48 cases but only 3/30 controls (odds ratio, 4.1; P = .02). Positive and negative controls yielded expected results. CONCLUSION C pneumoniae infection can reduce trophoblast invasion into the uterine wall and is associated with preeclampsia. Further investigation of the mechanisms by which C pneumoniae induces trophoblast dysfunction, and the identification of therapies to prevent adverse outcomes attributed to trophoblast dysfunction, are warranted.
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Nyström-Rosander C, Frisk P, Edvinsson M, Hjelm E, Thelin S, Friman G, Ilbäck NG. Thoracic aortic aneurysm patients with Chlamydophila pneumoniae infection showed a shift in trace element levels in serum and diseased aortic tissue. J Trace Elem Med Biol 2009; 23:100-6. [PMID: 19398057 DOI: 10.1016/j.jtemb.2009.01.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2008] [Revised: 11/18/2008] [Accepted: 01/15/2009] [Indexed: 12/19/2022]
Abstract
Few studies have been performed on trace elements in tissues and serum in cardiovascular disease and none in aortic aneurysm. In this study the concentrations of 10 trace elements were determined in serum and aneurysmatic aortic tissue from 23 patients undergoing thoracic surgery. Macroscopically, normal thoracic aortic tissue specimens from 10 forensic autopsies and serum from 23 healthy blood donors served as controls. DNA from the intracellular respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), which may be involved in the pathogenesis of atherosclerosis, was found in 26% (6/23) of the patients but in none of the controls. The serum copper/zinc ratio, a well-known marker of ongoing infection and/or inflammation, was higher (26%, p<0.001) in aneurysm patients. C. pneumoniae requires iron for its growth. In our aneurysm patients iron was higher in serum (by 54%, p<0.001) and aneurysmal tissue (by 60%, p<0.001). Although calcium was lower in patient sera (by 8%, p<0.001), it tended to be higher (by 20%, ns) in aneurysmatic tissue. In addition, mercury concentrations in serum and aneurysmatic tissue were positively correlated (r=0.51, p<0.05). Moreover, C. pneumoniae-positive aneurysmatic tissues had lower concentrations of manganese (46%, p<0.05) and zinc (26%, ns) but a higher concentration of mercury (50%, p<0.05) than C. pneumoniae-negative aneurysmatic tissues. In conclusion, aneurysm patients showed a shift in trace element levels in serum and in the diseased part of the aorta, the pattern being partly different in C. pneumoniae-positive compared with C. pneumoniae-negative patients. The results are compatible with active infection and/or inflammation, possibly initiated by C. pneumoniae.
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30
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Pesonen E, Tiirola T, Andsberg E, Jauhiainen M, Paldanius M, Persson K, Saikku P, Sarna S, Ohlin H, Leinonen M. Serum chlamydial lipopolysaccharide as a prognostic factor for a new cardiovascular event. Heart Lung 2008; 38:176-81. [PMID: 19486785 DOI: 10.1016/j.hrtlng.2008.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2008] [Revised: 06/11/2008] [Accepted: 06/20/2008] [Indexed: 10/21/2022]
Abstract
BACKGROUND Infections caused by Chlamydia pneumoniae are considered to participate in inflammatory processes leading to coronary artery disease. After a primary infection, the bacteria remain dormant intracellularly causing a chronic inflammatory stimulus. MATERIALS AND METHODS Blood samples were obtained from 235 patients with acute myocardial infarction (AMI) and 108 patients with unstable angina pectoris (UA). We evaluated the prognostic significance of bacterial and viral antibody titers, serum troponin T, C-reactive protein, and chlamydial lipopolysaccharide (cLPS) concentrations during acute coronary syndrome of patients with AMI and UA for cardiovascular death and new UA and AMI that required hospital care during a 6-year follow-up. RESULTS Serum cLPS levels correlated with C-reactive protein and serum troponin T concentrations during acute coronary events. Patients with AMI had significantly higher serum concentration of cLPS compared with patients with UA. Enterovirus antibody titers and cholesterol-lowering therapy at admission of the index event were negatively correlated with cLPS concentration (r = -.198, P = .0003 and r = -.26, P = .019, respectively). The presence of circulating cLPS was associated with a hazard ratio of 2.04 for a new cardiovascular event during the follow-up period (P = .006). The area under the curve in the receiver operating graph was .572. CONCLUSION cLPS is evidently liberated from the infected atherosclerotic tissue during an acute coronary event. Our study supports the view that inflammation caused by C. pneumoniae infection is an important but as yet poorly understood factor in the development of atherosclerosis and may play a role in acute vascular events.
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Affiliation(s)
- Erkki Pesonen
- Pediatric Cardiology, University Hospital of Lund, Getingevägen 4, Lund SE-221 85, Sweden
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Abstract
Chlamydiae are important intracellular bacterial pathogens of vertebrates. In the last years, novel members of this group have been discovered: Parachlamydia acanthamoebae and Simkania negevensis seems to be emerging respiratory human pathogens, while Waddlia chondrophila might be a new agent of bovine abortion. Various species have been showed to infect also the herpetofauna and fishes, and some novel chlamydiae are endosymbionts of arthropods. In addition, molecular studies evidenced a huge diversity of chlamydiae from both environmental and clinical samples, most of such a diversity could be formed by novel lineages of chlamydiae. Experimental studies showed that free-living amoebae may support multiplication of various chlamydiae, then could play an important role as reservoir/vector of chlamydial infections. Here we reviewed literature data concerning chlamydial infections, with a particular emphasis on the novely described chlamydial organisms.
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Affiliation(s)
- Daniele Corsaro
- Retrovirology Laboratory, Centre Hospitalier de Luxembourg, Luxembourg
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Bunk S, Susnea I, Rupp J, Summersgill JT, Maass M, Stegmann W, Schrattenholz A, Wendel A, Przybylski M, Hermann C. Immunoproteomic identification and serological responses to novel Chlamydia pneumoniae antigens that are associated with persistent C. pneumoniae infections. THE JOURNAL OF IMMUNOLOGY 2008; 180:5490-8. [PMID: 18390732 DOI: 10.4049/jimmunol.180.8.5490] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The controversial discussion about the role of Chlamydia pneumoniae in atherosclerosis cannot be solved without a reliable diagnosis that allows discrimination between past and persistent infections. Using a proteomic approach and immunoblotting with human sera, we identified 31 major C. pneumoniae Ags originating from 27 different C. pneumoniae proteins. More than half of the proteins represent Chlamydia Ags not described previously. Using a comparative analysis of spot reactivity Pmp6, OMP2, GroEL, DnaK, RpoA, EF-Tu, as well as CpB0704 and CpB0837, were found to be immunodominant. The comparison of Ab-response patterns of sera from subjects with and without evidence for persisting C. pneumoniae, determined by multiple PCR analysis of PBMC and vasculatory samples, resulted in differential reactivity for 12 proteins, which is not reflected by reactivity of the sera in the microimmunofluorescence test, the current gold standard for serodiagnosis. Although reactivity of sera from PCR-positive donors was increased toward RpoA, MOMP, YscC, Pmp10, PorB, Pmp21, GroEL, and Cpaf, the reactivity toward YscL, Rho, LCrE, and CpB0837 was decreased, reflecting the altered protein expression of persisting C. pneumoniae in vitro. Our data provide the first evidence of a unique Ab-response pattern associated with persistent C. pneumoniae infections, which is a prerequisite for the serological determination of persistently infected patients.
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Affiliation(s)
- Sebastian Bunk
- Department of Biochemical Pharmacology, University of Konstanz, Konstanz, Germany
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Ciervo A, Mancini F, Sale P, Russo A, Cassone A. Real-Time Polymerase Chain Reaction and Laser Capture Microdissection: An Efficient Combination Tool for Chlamydophila Pneumoniae DNA Quantification and Localization of Infection in Atherosclerotic Lesions. Int J Immunopathol Pharmacol 2008; 21:421-8. [DOI: 10.1177/039463200802100222] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Chlamydophila pneumoniae has been implicated in atherosclerosis, but the role of this obligate intracellular pathogen in the development of the above pathology is still unclear. In particular, its presence and quantitative distribution within lesional areas has not yet been defined. We studied 18 carotid biopsies obtained from patients undergoing endoartherectomy. By laser microdissection (LCM), two different sites (intra-plaque and plaque-adjacent areas) were taken from each lesion, and the presence and quantity of the pathogen DNA were determined by real-time polymerase chain reaction (Real-time PCR). A total of 8 plaques, exclusively, from patients with unstable angina, were positive in real-time PCR. The bacterial DNA was detected in both lesional areas of 3 plaques which contained the highest number of DNA copies (1,900 to 2,200 copy numbers), while C. pneumoniae DNA was detected only in the intra-plaque area of the other 5 positive (500 to 1,600 copy numbers). No C. pneumoniae DNA was found in the other 10 plaques of which 6 were from patients with unstable angina and 4 from stable angina patients. No DNA from Helicobacter pylori or Cytomegalovirus was found in any plaque. This is the first report where both the target lesion and an adjacent reference site were evaluated for the presence of C. pneumoniae DNA by the combination of LCM and Real-time PCR assays. The integration of these two methodologies offer an excellent tool for in situ studies and may help to elucidate the putative role of C. pneumoniae in atherosclerosis.
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Affiliation(s)
| | | | - P. Sale
- IRCCS San Raffaele Pisana, Roma
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Parratt J, Tavendale R, O'Riordan J, Parratt D, Swingler R. Chlamydia pneumoniae-specific serum immune complexes in patients with multiple sclerosis. Mult Scler 2008; 14:292-9. [DOI: 10.1177/1352458507083188] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The significance of Chlamydia pneumoniae infection in patients with multiple sclerosis (MS) is unclear. We determined the frequency of serum C. pneumoniae-specific immune complexes in patients with MS, neurological (OND) and healthy controls in a blinded, cross-sectional study. C. pneumoniae immune complexes were detected in 24% (38/156) of MS patients, 16% (11/69) of OND and 15% (77/499) of healthy controls. The odds ratio for all MS patients was 3.95 (95% CI: 2.15 to 7.24; P < 0.0001) accounting for the covariates: sex, age, socio-economic status and area of residence. The odds ratio for recently diagnosed MS patients was 4.33 (95% CI: 1.76 to 10.64; P = 0.001). Systemic C. pneumoniae infection is more frequent in MS patients than the healthy population and occurs early in the course of the disease. Multiple Sclerosis 2007; 14: 292—299. http://msj.sagepub.com
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Affiliation(s)
- John Parratt
- Department of Neurology, University of Sydney, Blackburn Building, Camperdown, Sydney, NSW 2006, Australia,
| | - Roger Tavendale
- Department of Cardiovascular Epidemiology, University of Dundee, Dundee, UK
| | | | - David Parratt
- Department of Microbiology, Tayside University Hospitals, Dundee, UK
| | - Robert Swingler
- Department of Neurology, Tayside University Hospitals, Dundee, UK
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Abstract
Cardiovascular disease, resulting from atherosclerosis, is a leading cause of global morbidity and mortality. Genetic predisposition and classical environmental risk factors explain much of the attributable risk for cardiovascular events in populations, but other risk factors for the development and progression of atherosclerosis, which can be identified and modified, may be important therapeutic targets. Infectious agents, such as Chlamydia pneumoniae, have been proposed as contributory factors in the pathogenesis of atherosclerosis. In the present review, we consider the experimental evidence that has accumulated over the last 20 years evaluating the role of C. pneumoniae in atherosclerosis and suggest areas for future research in this field.
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Miyashita N, Obase Y, Fukuda M, Shouji H, Yoshida K, Ouchi K, Oka M. Evaluation of the diagnostic usefulness of real-time PCR for detection of Chlamydophila pneumoniae in acute respiratory infections. J Infect Chemother 2007; 13:183-7. [PMID: 17593507 DOI: 10.1007/s10156-007-0509-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2006] [Accepted: 02/01/2007] [Indexed: 11/24/2022]
Abstract
We investigated whether a real-time polymerase chain reaction (PCR) test is a useful diagnostic tool for identifying individuals with acute respiratory Chlamydophila pneumoniae infections. Nasopharyngeal swab specimens and peripheral blood mononuclear cells (PBMCs) from 100 patients with acute respiratory tract infections and 140 asymptomatic healthy subjects (controls) were analyzed using real-time PCR, culture, and serology for the detection of C. pneumoniae. Six patients had serological results indicating acute C. pneumoniae infections. C. pneumoniae DNA was detected in respiratory samples from eight patients (three of these cases were serologically confirmed as having C. pneumoniae infections) and four controls. The amount of C. pneumoniae DNA present in the real-time PCR for the samples was calculated, and no significant differences in the amount of DNA between symptomatic and asymptomatic subjects were found. On the other hand, traces of C. pneumoniae DNA were detected in PBMCs from eight patients, but this was confirmed in PBMCs from only seven of these patients. Only one patient had both respiratory and blood samples that were positive. C. pneumoniae DNA was also detected in samples from six controls, but no significant differences in the amount of C. pneumoniae DNA were observed between patients and controls. The present quantitative real-time PCR assay does not seem to be a useful method for differentiating between C. pneumoniae acute infections and persistent ones or nasopharyngeal carriage. In addition, the detection of C. pneumoniae DNA in PBMCs does not seem to be a suitable method for the diagnosis of acute respiratory C. pneumoniae infections.
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Affiliation(s)
- Naoyuki Miyashita
- Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
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Wang SS, Tondella MLC, Bajpai A, Mathew AG, Mehranpour P, Li W, Kacharava AG, Fields BS, Austin H, Zafari AM. Circulating Chlamydia pneumoniae DNA and advanced coronary artery disease. Int J Cardiol 2006; 118:215-9. [PMID: 17023075 DOI: 10.1016/j.ijcard.2006.07.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2006] [Revised: 05/24/2006] [Accepted: 07/15/2006] [Indexed: 12/21/2022]
Abstract
BACKGROUND Chlamydia pneumoniae (C. pneumoniae) has been linked to atherosclerosis. Detection of this pathogen in peripheral blood cells may be valuable in the diagnosis of disease state. This study aimed to evaluate the prevalence of circulating C. pneumoniae DNA and its relationship with severity and extent of coronary artery disease (CAD). METHODS Blood samples from 269 patients undergoing coronary angiography were collected. The presence of circulating C. pneumoniae DNA was determined by real-time PCR assay. Data regarding coronary risk factors and severity and extent of CAD were collected. Severity and extent of CAD was defined by the number of major epicardial coronary arteries with >50% stenosis and by the Duke jeopardy score. RESULTS Sixteen of 269 specimens (5.9%) from the study cohort were positive for C. pneumoniae DNA. Thirteen specimens among 149 samples from patients with multi-vessel disease (8.7%) were positive for C. pneumoniae DNA compared with 3 of 120 (2.5%) among patients without multi-vessel CAD. The prevalence of circulating C. pneumoniae DNA was significantly associated with multi-vessel disease. The odds ratio was 5.1 (P=0.02) after adjustment for conventional risk factors. CONCLUSIONS Presence of circulating C. pneumoniae DNA is associated with advanced CAD, suggesting C. pneumoniae infection as a contributing factor to progression of coronary atherosclerosis.
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Affiliation(s)
- Shaoshan S Wang
- Division of Cardiology, Emory University, Atlanta, GA 30322, USA
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Dettmeyer R, Stiel M, Madea B. Chlamydial heat-shock protein 60 : A marker for chronic infection with Chlamydia Pneumoniae in atherosclerosis: Investigation of atherosclerotic coronary arteries by immunocytochemistry. Forensic Sci Med Pathol 2006; 2:173-8. [PMID: 25868695 DOI: 10.1007/s12024-006-0006-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2006] [Indexed: 11/29/2022]
Abstract
Worldwide, ischemic heart disease is an important cause of death and there is an increasing number of pointers toward a causative connection between Chlamydia pneumoniae and atherosclerosis. The presence, localization, and relationship to atheroma of Chlamydial heat-shock protein 60 (cHsp60) in coronary tissue was investigated by immunocytochemical methods and by different investigators. In the present study, for the first time, arterial segments, including the whole course of the great coronary arteries from proximal to distal, were investigated by immunocytochemistry to detect cHsp60. Specimens from coronary arteries of 46 autopsy cases (17 females, 29 males; mean age: 62.7 years, SD 17.9 years) were examined (480 paraffin-embedded samples; 11 sites from each case). Different fixatives were used for the specimens taken at autopsy. Immunocytochemical staining was done using an anti-cHsp60 antibody (Affinity Bioreagents Inc.) and a modified Labeled-Strept-Avidine-Biotin-staining protocol (DAKO). The localization of signals by site of predilection in the course of coronary vessels and by coincidence with specific structural characteristics, was detected by light microscopy. Detection of cHsp60 was possible in 30 of 46 (65.2%) individuals (minimum one sample) and in 87 of 480 specimens (18.1%). The distribution of the signals was correlated to the intensity of atherosclerosis (mild to middle) and a decreasing frequency from proximal to distal arterial segments was found. Macroscopically, nonatherosclerotic vessels presented cHsp60 only occasionally. In accordance with recent publications, cHsp60 was detected in foam cells and macrophages, cell-poor regions, and thickened intimal layers, and more rarely in inflammatory infiltrates and calcified areas. According to previous studies, a distribution independent from atherosclerotic lesions was not found. Detection of cHsp60 was superior using Notox(®) (Earth Industries) as a fixative in comparison with buffered formaldehyde.
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Affiliation(s)
- Reinhard Dettmeyer
- Institute of Legal Medicine, Rheinische Friedrich-Wilhems-University, Stiftsplatz 12, D-53111, Bonn, Germany,
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Cuffini C, Alberto Guzmán L, Villegas N, Eduardo Alonso C, Martínez-Riera L, Rodríguez-Fermepín M, Carolina Entrocassi A, Pilar Adamo M, Pedranti M, Zapata M. Isolation of Chlamydophila pneumoniae from atheromas of the carotid artery and their antibiotics susceptibility profile. Enferm Infecc Microbiol Clin 2006; 24:81-5. [PMID: 16545314 DOI: 10.1157/13085013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND Atherosclerosis is pathogenically similar to a chronic inflammatory response. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis. Chlamydophila pneumoniae has been suggested to play a role in the origin of PAD. OBJECTIVE To determine whether C. pneumoniae is present in atherosclerosis lesions of the carotid artery wall in patients with PAD through several diagnostic methods and to characterize C. pneumoniae susceptibility profiles. METHODS The presence of C. pneumoniae in 9 tissue samples from atherosclerotic lesions obtained by carotid endarterectomy was investigated by 3 methods. Karnofsky-fixed specimens were examined by transmission electron microscopy (TEM), isolation of C. pneumoniae was attempted in LLCMK2 cell structure (ICC), and the presence of chlamydial DNA was investigated by polymerase chain reaction (PCR). The in vitro activities of azithromycin, roxithromycin and penicillin were tested in 4 isolations and the reference strain of C. pneumoniae (AR39). RESULTS C. pneumoniae was detected in atherosclerotic plaques from 4 patients with PAD. The pathogen was identified by TEM, PCR and ICC. We report data of the in vitro susceptibility of 4 strains. These strains did not differ from respiratory AR39 strain in their susceptibility patterns to azithromycin, roxithromycin and penicillin. CONCLUSIONS C. pneumoniae is frequently found in the advanced carotid atherosclerotic lesions of patients undergoing endarterectomy. Although these findings do not establish causality in carotid artery atherosclerosis, they should stimulate investigation of the possible causal or pathogenic role of C. pneumoniae. Notably, the profiles of antibiotic susceptibility of C. pneumoniae isolated from 4 of the patients did not differ from those of the reference strain.
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Affiliation(s)
- Cecilia Cuffini
- Instituto de Virología Dr. J.M. Vanella, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
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Cirino F, Webley WC, West C, Croteau NL, Andrzejewski C, Stuart ES. Detection of Chlamydia in the peripheral blood cells of normal donors using in vitro culture, immunofluorescence microscopy and flow cytometry techniques. BMC Infect Dis 2006; 6:23. [PMID: 16472397 PMCID: PMC1386677 DOI: 10.1186/1471-2334-6-23] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2005] [Accepted: 02/10/2006] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Chlamydia trachomatis (Ct) and Chlamydia pneumoniae (Cp) are medically significant infectious agents associated with various chronic human pathologies. Nevertheless, specific roles in disease progression or initiation are incompletely defined. Both pathogens infect established cell lines in vitro and polymerase chain reaction (PCR) has detected Chlamydia DNA in various clinical specimens as well as in normal donor peripheral blood monocytes (PBMC). However, Chlamydia infection of other blood cell types, quantification of Chlamydia infected cells in peripheral blood and transmission of this infection in vitro have not been examined. METHODS Cp specific titers were assessed for sera from 459 normal human donor blood (NBD) samples. Isolated white blood cells (WBC) were assayed by in vitro culture to evaluate infection transmission of blood cell borne chlamydiae. Smears of fresh blood samples (FB) were dual immunostained for microscopic identification of Chlamydia-infected cell types and aliquots also assessed using Flow Cytometry (FC). RESULTS ELISA demonstrated that 219 (47.7%) of the NBD samples exhibit elevated anti-Cp antibody titers. Imunofluorescence microscopy of smears demonstrated 113 (24.6%) of samples contained intracellular Chlamydia and monoclonals to specific CD markers showed that in vivo infection of neutrophil and eosinophil/basophil cells as well as monocytes occurs. In vitro culture established WBCs of 114 (24.8%) of the NBD samples harbored infectious chlamydiae, clinically a potentially source of transmission, FC demonstrated both Chlamydia infected and uninfected cells can be readily identified and quantified. CONCLUSION NBD can harbor infected neutrophils, eosinophil/basophils and monocytes. The chlamydiae are infectious in vitro, and both total, and cell type specific Chlamydia carriage is quantifiable by FC.
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Affiliation(s)
- Frances Cirino
- Department of Microbiology, University of Massachusetts, Amherst Massachusetts, 01003, USA
| | - Wilmore C Webley
- Department of Microbiology, University of Massachusetts, Amherst Massachusetts, 01003, USA
| | - Corrie West
- Department of Microbiology, University of Massachusetts, Amherst Massachusetts, 01003, USA
| | | | - Chester Andrzejewski
- Department of Microbiology, University of Massachusetts, Amherst Massachusetts, 01003, USA
- Department of Transfusion Medicine Baystate Medical Center, Springfield, Massachusetts, 01199, USA
| | - Elizabeth S Stuart
- Department of Microbiology, University of Massachusetts, Amherst Massachusetts, 01003, USA
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Elkind MSV, Tondella MLC, Feikin DR, Fields BS, Homma S, Di Tullio MR. Seropositivity to Chlamydia pneumoniae is associated with risk of first ischemic stroke. Stroke 2006; 37:790-5. [PMID: 16424371 DOI: 10.1161/01.str.0000202624.89869.e9] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND PURPOSE Serologic evidence of infection with Chlamydia pneumoniae has been associated with cardiovascular disease, but its relationship with stroke risk remains uncertain. The objective of this study is to determine whether serological evidence of C pneumoniae infection is associated with risk of ischemic stroke. METHODS A population-based case-control study was performed in an urban, multiethnic population. Cases (n=246) had first ischemic stroke, and controls (n=474) matched for age, sex, and race-ethnicity were derived through random-digit dialing. Titers of C pneumoniae-specific IgG and IgA antibodies were measured using microimmunofluorescence, and positive titers were prospectively defined. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs adjusting for medical, behavioral, and socioeconomic factors. RESULTS Mean age among cases was 72.3+/-9.7 years; 50.8% were women. Elevated C pneumoniae IgA titers were associated with increased risk of ischemic stroke after adjusting for hypertension, diabetes mellitus, current cigarette use, atrial fibrillation, and levels of high-density lipoprotein and low-density lipoprotein (adjusted OR, 1.5; 95% CI, 1.0 to 2.2). Elevated IgG titers were not associated with stroke risk (adjusted OR, 1.2; 95% CI, 0.8 to 1.8). There was a trend toward an association of elevated IgA titers with atherosclerotic and lacunar stroke but less so cardioembolic or cryptogenic subtypes. CONCLUSIONS Serologic evidence of C pneumoniae infection is associated with ischemic stroke risk. IgA titers may be a better marker of risk than IgG. This association is independent of other stroke risk factors and is present for atherosclerotic, lacunar, and cardioembolic subtypes. Further studies of the effect of C pneumoniae on stroke risk are warranted.
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Affiliation(s)
- Mitchell S V Elkind
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
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Tiirola T, Jaakkola A, Bloigu A, Paldanius M, Sinisalo J, Nieminen MS, Silvennoinen-Kassinen S, Saikku P, Jauhiainen M, Leinonen M. Novel enzyme immunoassay utilizing lipopolysaccharide-binding protein as a capture molecule for the measurement of chlamydial lipopolysaccharide in serum. Diagn Microbiol Infect Dis 2006; 54:7-12. [PMID: 16290027 DOI: 10.1016/j.diagmicrobio.2005.09.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2005] [Indexed: 10/25/2022]
Abstract
Chlamydia pneumoniae causes respiratory tract infections. It has a tendency to cause persistent infections, which have been associated with several chronic diseases (e.g., atherosclerosis). At present, there is no reliable method for the diagnosis of chronic C. pneumoniae infection. We developed a novel enzyme immunoassay (EIA) for the quantification of chlamydial lipopolysaccharide (cLPS) in human serum. Serum cLPS was solubilized with detergent and then captured by LPS-binding protein (LBP). LBP-LPS complexes were bound to the solid phase with anti-cLPS monoclonal antibody, and the bound complexes were detected with anti-LBP antibodies. The new method was used to quantify serum cLPS in acute coronary syndrome (ACS) patients (n = 102) and their healthy controls. cLPS was detected in 77.5% of ACS patients and in 52% of controls (P < .001) with geometric mean concentrations of 1.87 and 0.61 microg/mL (P < .001), respectively. The novel cLPS EIA method will provide a potential diagnostic tool for C. pneumoniae infection.
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Affiliation(s)
- Terttu Tiirola
- Department of Molecular Medicine, National Public Health Institute, Biomedicum, PO Box 104, FIN-00251 Helsinki, Finland.
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Podsiadły E, Przyłuski J, Kwiatkowski A, Kruk M, Wszoła M, Nosek R, Rowiński W, Ruzyłło W, Tylewska-Wierzbanowska S. Presence of Chlamydia pneumoniae in patients with and without atherosclerosis. Eur J Clin Microbiol Infect Dis 2005; 24:507-13. [PMID: 16133407 DOI: 10.1007/s10096-005-1380-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Data published over the past decade show that Chlamydia pneumoniae is likely associated with the development of atherosclerosis. The aim of this study was to ascertain whether C. pneumoniae infections occur more frequently in patients with atherosclerosis than in healthy subjects. A total of 517 persons were studied. Serum samples, leukocytes, and tissue samples were assayed for the presence of C. pneumoniae-specific IgG and IgA antibodies and C. pneumoniae DNA. C. pneumoniae DNA was found in renal, iliac, and brachial vessels, but it was not detected in radial arteries. C. pneumoniae DNA was found most often in directional coronary atherectomy tissue specimens (11/41, 26.8%), but it was also found in the leukocytes of 14.9% (28/188) of patients with atherosclerosis and 24.6% (28/114) of patients without atheroma changes in vessels. Specific IgG and IgA antibodies were present in 63.8 and 49.9% of atheroma patients, respectively. The prevalence of C. pneumoniae antibodies differs significantly in patients with and without atherosclerosis (for IgG, p=0.002, and for IgA, p=0.006). The identification of persons with chlamydial infection of atherosclerotic arteries necessitates the examination of vascular tissues obtained during revascularization procedures. Serological investigation alone cannot identify individuals with vascular chlamydial infections. Detection of C. pneumoniae DNA in peripheral blood mononuclear cells does not seem to be the exclusive marker of persistent vascular infection. A more easily accessible parameter that allows prediction of chlamydial vascular infection is required.
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Affiliation(s)
- E Podsiadły
- National Institute of Hygiene, Laboratory of Rickettsiae, Chlamydiae and Enzotic Spirochetes, Chocimska 24, 00-791, Warsaw, Poland.
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Franciotta D, Zardini E, Bergamaschi R, Grimaldi LM, Andreoni L, Cosi V. Analysis of Chlamydia pneumoniae-specific oligoclonal bands in multiple sclerosis and other neurologic diseases. Acta Neurol Scand 2005; 112:238-41. [PMID: 16146493 DOI: 10.1111/j.1600-0404.2005.00407.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Paired serum and cerebrospinal fluid (CSF) specimens were investigated for Chlamydia pneumoniae-specific oligoclonal bands (OCBs) to determine band specificity in multiple sclerosis (MS). MATERIAL AND METHODS Serum and CSF samples were collected from patients with relapsing-remitting MS (n = 56), other inflammatory (n = 18) or non-inflammatory (n = 15) neurologic diseases, and from 10 healthy controls. OCBs were determined with affinity immunoblotting of C. pneumoniae-specific IgG onto antigen-coated nitrocellulose paper after protein separation with agarose isoelectric focusing. RESULTS Chlamydia pneumoniae-specific OCBs were present in 5 of 56 patients with MS, and in 3 of 18 patients with other inflammatory neurologic diseases. CONCLUSIONS The intrathecal production of C. pneumoniae-specific oligoclonal IgG occurs in a minority of patients with MS. This intrathecal anti-C. pneumoniae reactivity is likely part of a polyspecific humoral immune response in MS.
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Affiliation(s)
- D Franciotta
- Laboratory of Neuroimmunology, IRCCS, Foundation Neurological Institute C. Mondino, University of Pavia, Pavia, Italy.
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Teig N, Anders A, Schmidt C, Rieger C, Gatermann S. Chlamydophila pneumoniae and Mycoplasma pneumoniae in respiratory specimens of children with chronic lung diseases. Thorax 2005; 60:962-6. [PMID: 16143584 PMCID: PMC1747249 DOI: 10.1136/thx.2005.041004] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Persistent infection with Mycoplasma pneumoniae and Chlamydophila pneumoniae has been implicated in the progression or induction of asthma and chronic obstructive pulmonary disease. Evidence for this hypothesis has been obtained in adults either by serological methods or by direct pathogen detection using invasive procedures. METHODS We investigated nasal brush specimens and induced sputum from 38 children with stable chronic lung disease (asthma, n = 26; chronic bronchitis n = 12) and from 42 healthy controls for the presence of M pneumoniae or C. pneumoniae DNA by polymerase chain reaction (PCR) using nested primers. RESULTS None of the controls but 23.6% and 10.5% of the children with lung disease had positive PCR for C pneumoniae (p = 0.001) and M pneumoniae (p = 0.044) respectively. Significantly more children with non-atopic asthma than with atopic asthma were positive for C pneumoniae or M pneumoniae (4/8 v 1/18; p = 0.018). There were no unwanted side effects from sputum induction. No correlation was found between detection of Chlamydophila and severity of lung disease. Colonisation with both organisms had occurred before adulthood in a significant proportion of children with stable chronic lung diseases. CONCLUSION Combining nasal brush specimens with induced sputum may be a useful non-invasive method for studying the role of C pneumoniae and M pneumoniae infection in children with different chronic lung diseases.
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Affiliation(s)
- N Teig
- Children's Hospital of Ruhr University, St Josef Hospital, Bochum, Germany.
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Skelding KA, Hickey DK, Horvat JC, Bao S, Roberts KG, Finnie JM, Hansbro PM, Beagley KW. Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respiratory tract infection. Vaccine 2005; 24:355-66. [PMID: 16153755 DOI: 10.1016/j.vaccine.2005.07.104] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2005] [Accepted: 07/27/2005] [Indexed: 02/08/2023]
Abstract
Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TCI routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TCI protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific IgA in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN>TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNgamma mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNgamma levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7,000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1,500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNgamma production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.
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Affiliation(s)
- Kathryn A Skelding
- Discipline of Immunology and Microbiology, School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia
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Wolf K, Fischer E, Hackstadt T. Degradation of Chlamydia pneumoniae by peripheral blood monocytic cells. Infect Immun 2005; 73:4560-70. [PMID: 16040967 PMCID: PMC1201216 DOI: 10.1128/iai.73.8.4560-4570.2005] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2005] [Revised: 03/30/2005] [Accepted: 04/04/2005] [Indexed: 11/20/2022] Open
Abstract
Chlamydia pneumoniae is a common human respiratory pathogen that has been associated with a variety of chronic diseases, including atherosclerosis. The role of this organism in the pathogenesis of atherosclerosis remains unknown. A key question is how C. pneumoniae is transferred from the site of primary infection to a developing atherosclerotic plaque. It has been suggested that circulating monocytes could be vehicles for dissemination of C. pneumoniae since the organism has been detected in peripheral blood monocytic cells (PBMCs). In this study we focused on survival of C. pneumoniae within PBMCs isolated from the blood of healthy human donors. We found that C. pneumoniae does not grow and multiply in cultured primary monocytes. In C. pneumoniae-infected monocyte-derived macrophages, growth of the organism was very limited, and the majority of the bacteria were eradicated. We also found that the destruction of C. pneumoniae within infected macrophages resulted in a gradual diminution of chlamydial antigens, although some of these antigens could be detected for days after the initial infection. The detected antigens present in infected monocytes and monocyte-derived macrophages represented neither chlamydial inclusions nor intact organisms. The use of {N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]}-6-aminocaproyl-d-erythro-sphingosine as a vital stain for chlamydiae proved to be a sensitive method for identifying rare C. pneumoniae inclusions and was useful in the detection of even aberrant developmental forms.
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Affiliation(s)
- Katerina Wolf
- Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, NIAID, NIH, Rocky Mountain Laboratories, Hamilton, MT 59840, USA
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Taylor-Robinson D, Sharif AW, Dhanjal NS, Taylor-Robinson SD. Chlamydia pneumoniae infection is an unlikely cause of primary biliary cirrhosis. J Hepatol 2005; 42:779-80. [PMID: 15826729 DOI: 10.1016/j.jhep.2004.08.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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Tositti G, Rassu M, Fabris P, Giordani M, Cazzavillan S, Reatto P, Zoppelletto M, Bonoldi M, Baldo V, Manfrin V, de Lalla F. Chlamydia pneumoniae infection in HIV-positive patients: prevalence and relationship with lipid profile. HIV Med 2005; 6:27-32. [PMID: 15670249 DOI: 10.1111/j.1468-1293.2005.00261.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVES The aims of this study were to evaluate the prevalence and impact of Chlamydia pneumoniae infection in HIV-positive patients and to establish the relationship between C. pneumoniae infection and lipid profile. METHODS Detection of C. pneumoniae was by polymerase chain reaction (PCR) on Peripheral Blood Mononuclear Cells (PBMCs) collected from 97 HIV-positive patients. Samples were collected after overnight fast in EDTA-treated tubes. On the same day, patients were also tested for routine chemistry, HIV viral load, CD3, CD8 and CD4 cell counts and lipid profile [cholesterol, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs) and triglycerides]. RESULTS The overall prevalence of C. pneumoniae was 39%. The prevalence of C. pneumoniae was inversely related to the CD4 lymphocyte count (P=0.03). In the naive group, C. pneumoniae-positive patients had both significantly higher HIV load (71 021+/-15 327 vs. 14 753+/-14 924 HIV-1 RNA copies/mL; P=0.03) and lower CD4 cell count (348.0+/-165.4 vs. 541.7+/-294.8; P=0.04) than C. pneumoniae-negative patients. Moreover, treatment-naive patients with C. pneumoniae infection had significantly higher mean levels of cholesterol (185.3+/-56.2 vs. 124.8+/-45.9 mg/dL; P=0.01), triglycerides (117.2+/-74.7 vs. 68+/-27.6 mg/dL; P=0.04) and LDL (122.4+/-60.1 vs. 55.6+/-58 mg/dL; P=0.05) than C. pneumoniae-negative patients. CONCLUSIONS These data indicate that, in HIV-positive subjects, C. pneumoniae infection is relatively frequent and is associated with both low CD4 cell count and high HIV load. Furthermore, C. pneumoniae appears to be associated with hyperlipidaemia and might therefore represent a further risk factor for cardiovascolar disease in HIV-positive patients.
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Affiliation(s)
- G Tositti
- Department of Infectious Diseases and Tropical Medicine, San Bortolo Hospital, Vincenza, Italy
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