Cystic echinococcosis is speculated to exert several immune-evasion strategies involving autoimmune-phenomena. We evaluated the hypothesizes that the prevalence of autoantibodies increases in the sera of CE patients that may evidence the association between the parasite and autoimmune diseases. Sera from 63 subjects at distinct types of CE cyst fertility were investigated for antinuclear antibodies (ANA), and anti-CCP antibodies. Plasma levels and cellular production of IL-17A cytokine were specifically defined as being assumed to prime for autoimmunity. Healthy-controls were age and gender-matched to test sera. ANA expressions inside the surgically removed metacestode and adventitial layer were also assayed. Out of 63 patients, 35 % had fertile highly viable cysts (group-1), 41 % had fertile low viable cysts (group-2) and 24 % had non-fertile cysts (group-3). A four-fold increase in ANA sera-levels was detected in group-1 compared with their controls (p-value 0.001) while anti-CCP levels were of insignificant differences. In group-2 and group-3, no significant differences were detected between ANA and anti-CCP sera-levels in CE patients and their controls. IL-17A sera-levels in group-1 and group- 2 were significantly higher than their healthy-controls while being of insignificant differences in group-3, p-value= 0.300. No association was detected between sera-levels of IL-17A and ANA as well as anti-CCP antibodies. Interestingly, relative IL-17A cellular expression associated positive ANA deposition in the parasite cells and adventitial layer. Collectively, based on the parasite fertility, IL-17A and ANA seemed to be involved in the host immune defenses against CE. There is no association between CE and anti-CCP antibodies.

Candidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.

Autoimmune uveitis is a major cause of blindness in humans. Activation of retina-specific autoreactive T cells by commensal microbiota has been shown to trigger uveitis in mice. Although a culprit microbe and/or its immunogenic antigen remains to be identified, studies from inducible and spontaneous mouse models suggest the potential of microbiota-modulating therapies for treating ocular autoimmune disease. In this review, we summarize recent findings on the contribution of microbiota to T cell-driven, tissue-specific autoimmunity, with an emphasis on autoimmune uveitis, and analyze microbiota-altering interventions, including antibiotics, probiotics, and microbiota-derived metabolites (e.g., short-chain fatty acids), which have been shown to be effective in other autoimmune diseases. We also discuss the need to explore more translational animal models as well as to integrate various datasets (microbiomic, transcriptomic, proteomic, metabolomic, and other cellular measurements) to gain a better understanding of how microbiota can directly or indirectly modulate the immune system and contribute to the onset of disease. It is hoped that deeper understanding of these interactions may lead to more effective treatment interventions.

• animal models
• autoimmune uveitis
• microbiota
• multi-omic approach
• tissue-specific autoimmunity
• treatment intervention

• Autoimmunity
• Cytokines
• Dendritic cells
• Echinococcus granulosus
• Immunity
• Lymphocytes

Paracoccidioidomycosis, a primary fungal infection restricted to Latin America, is acquired by inhalation of fungal particles. The immunoregulatory mechanisms that control the severe and mild forms of paracoccidioidomycosis are still unclear. Indoleamine 2,3-dioxygenase (IDO), an IFN-γ induced enzyme that catalyzes tryptophan metabolism, can control host-pathogen interaction by inhibiting pathogen growth, T cell immunity and tissue inflammation.

In this study, we investigated the role of IDO in pulmonary paracoccidioidomycosis of susceptible and resistant mice. IDO was blocked by 1-methyl-dl-tryptophan (1MT), and fungal infection studied in vitro and in vivo. Paracoccidioides brasiliensis infection was more severe in 1MT treated than untreated macrophages of resistant and susceptible mice, concurrently with decreased production of kynurenines and IDO mRNA. Similar results were observed in the pulmonary infection. Independent of the host genetic pattern, IDO inhibition reduced fungal clearance but enhanced T cell immunity. The early IDO inhibition resulted in increased differentiation of dendritic and Th17 cells, accompanied by reduced responses of Th1 and Treg cells. Despite these equivalent biological effects, only in susceptible mice the temporary IDO blockade caused sustained fungal growth, increased tissue pathology and mortality rates. In contrast, resistant mice were able to recover the transitory IDO blockade by the late control of fungal burdens without enhanced tissue pathology.

Our studies demonstrate for the first time that in pulmonary paracoccidioidomycosis, IDO is an important immunoregulatory enzyme that promotes fungal clearance and inhibits T cell immunity and inflammation, with prominent importance to susceptible hosts. In fact, only in the susceptible background IDO inhibition resulted in uncontrolled tissue pathology and mortality rates. Our findings open new perspectives to understand the immunopathology of paracoccidioidomycosis, and suggest that an insufficient IDO activity could be associated with the severe cases of human PCM characterized by inefficient fungal clearance and excessive inflammation.

Immunoprotection to paracoccidiodomycosis, a systemic mycosis endemic in Latin America, is mediated by T cell immunity whereas immunosuppression characterizes the severe forms of the disease. Indoleamine 2,3-dioxygenase (IDO), an enzyme mainly induced by IFN-γ, catabolizes tryptophan along the kynurenines pathway. Tryptophan deficiency has been associated with reduced pathogen growth, while elevated levels of kynurenines with suppressed immune responses. In this study, the role of IDO in pulmonary paracoccidioidomycosis was investigated using resistant and susceptible mice. In both mouse strains, IDO blockade by 1-methyl tryptophan resulted in inefficient fungal clearance accompanied by enhanced T cell immunity. Despite these equivalent biological effects, only in susceptible mice IDO inhibition caused progressive fungal growth and tissue pathology resulting in increased mortality. Our findings demonstrate for the first time that IDO exert a yet unexplored immunoregulatory role in pulmonary paracoccidioidomycosis that can be particularly important in the severe cases of the disease.

• Animals
• Cytokines/metabolism
• Dendritic Cells/immunology
• Disease Susceptibility
• Host-Pathogen Interactions/immunology
• Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology
• Indoleamine-Pyrrole 2,3,-Dioxygenase/pharmacology
• Kynurenine/metabolism
• Lung/drug effects
• Lung/immunology
• Mice
• Paracoccidioidomycosis/immunology
• Paracoccidioidomycosis/microbiology

Innate and adaptive immune responses in neurodegenerative diseases have become recently a focus of research and discussions. Parkinson’s disease (PD) is a neurodegenerative disorder without known etiopathogenesis. The past decade has generated evidence for an involvement of the immune system in PD pathogenesis. Both inflammatory and autoimmune mechanisms have been recognized and studies have emphasized the role of activated microglia and T-cell infiltration. In this short review, we focus on dendritic cells, on their role in initiation of autoimmune responses, we discuss aspects of neuroinflammation and autoimmunity in PD, and we report new evidence for the involvement of neuromelanin in these processes.

• Animals
• Humans
• Immunity, Mucosal/immunology
• Interleukins/immunology
• Metagenome/immunology
• Mycoses/immunology
• Interleukin-22