• AMPKα
• Autophagy
• Baicalein
• CCDC88A
• Hepatitis B virus

• Flavanones/pharmacology
• Humans
• Autophagy/drug effects
• Hepatitis B virus/drug effects
• Hepatitis B Surface Antigens/metabolism
• Hepatitis B Surface Antigens/drug effects
• Scutellaria baicalensis/chemistry
• Hep G2 Cells
• Signal Transduction/drug effects
• Antiviral Agents/pharmacology
• Hepatitis B e Antigens/metabolism
• DNA, Viral/drug effects
• TOR Serine-Threonine Kinases/metabolism

• AMPKα
• ERα
• antiviral flavonoid
• baicalin
• hepatitis B virus
• hepatocyte nuclear factor

• Humans
• Flavonoids/pharmacology
• Estrogen Receptor alpha/metabolism
• Virus Replication/drug effects
• Hepatitis B virus/drug effects
• AMP-Activated Protein Kinases/metabolism
• Hep G2 Cells
• Signal Transduction/drug effects
• Down-Regulation/drug effects
• Antiviral Agents/pharmacology
• Molecular Docking Simulation

• HIV
• PD‐1
• hepatitis B
• immune checkpoint
• immune checkpoint inhibitors

• Animals
• Humans
• HIV Infections/drug therapy
• HIV Infections/immunology
• HIV Infections/virology
• HIV-1/drug effects
• HIV-1/immunology
• Immune Checkpoint Inhibitors/therapeutic use
• Immune Checkpoint Inhibitors/pharmacology
• Immunotherapy/methods
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Programmed Cell Death 1 Receptor/metabolism
• T-Lymphocytes/immunology
• Virus Latency/drug effects
• Virus Latency/immunology

• 109226-58-RGRL The Foundation for AIDS Research
• UM1 AI164560 NIAID NIH HHS
• 2026490 National Health and Medical Research Council
• 1 UM1 AI164560-01 National Institute of Allergy and Infectious Diseases
• 149990 National Health and Medical Research Council
• The Foundation for AIDS Research
• National Institute of Allergy and Infectious Diseases
• National Health and Medical Research Council

• STING
• host-directed
• infection
• itaconate
• pyroptosis
• therapeutic

• Humans
• COVID-19/immunology
• SARS-CoV-2
• Communicable Diseases/drug therapy
• Communicable Diseases/therapy
• Communicable Diseases/immunology
• Animals
• Antiviral Agents/therapeutic use

• immunometabolism
• immunopathology
• immunotherapy
• viral infection

• Humans
• Antibodies, Monoclonal/therapeutic use
• Pyrimethamine
• Sulfadiazine

• CD8+ T lymphocytes
• Hepatitis B virus
• Immune checkpoint inhibitors
• PD-1/PD-L1 inhibitors

• Humans
• Hepatitis B, Chronic/drug therapy
• Immune Checkpoint Inhibitors/adverse effects
• Programmed Cell Death 1 Receptor/therapeutic use
• Hepatitis B
• Hepatitis B virus/physiology
• CD8-Positive T-Lymphocytes
• Antiviral Agents/therapeutic use
• Antiviral Agents/pharmacology

• antiviral treatment
• hepatitis B virus (HBV)
• immunoprophylaxis
• peripheral blood monocellular cells (PBMC)
• risk factors
• vertical transmission

• BUPP ES84190031 University of Antioquia

• Humans
• Hepatitis B virus
• Hepatitis B
• Killer Cells, Natural
• Hepatitis B, Chronic
• Antiviral Agents/therapeutic use

• Horizon 2020

• cancer
• immunotherapy
• occult hepatitis B
• reactivation
• real-life study
• screening

• COVID-19
• aging
• exhaustion
• immunity
• infections
• senescence

• Aged
• Aging/pathology
• Cellular Senescence
• Humans
• Inflammation

• IRCCS Humanitas Research Hospital

• DNA damage
• T cells
• West Nile virus
• aging
• cytomegalovirus
• vaccination

• Adolescent
• Animals
• Cytomegalovirus
• Humans
• Mice
• Mice, Inbred BALB C
• Muromegalovirus
• Vaccination
• West Nile virus

• HHSN272200900059C NIAID NIH HHS
• R37 AG020719 NIA NIH HHS
• T32 AG058503 NIA NIH HHS
• National Institute of Allergy and Infectious Diseases
• U.S. Department of Energy
• University of Arizona
• Arizona Cancer Center
• Dartmouth College

Thus far, few studies have investigated the safety and efficacy of programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) antibodies in patients with hepatitis B virus (HBV)-related liver cancer.

To investigate the effect of combination therapy with programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) on HBV-related liver cancer.

Until January 31, 2022, liver cancer patients with hepatitis B surface antigen (HBsAg) or HBV DNA positivity, treated with PD-1 ICIs and TKIs combined with nucleoside analogs (NAs), were retrospectively reviewed. The correlation between the change in HBV DNA and HBsAg levels and tumor response was analyzed using the χ² test. Cox univariate and multivariate survival analyses and Kaplan–Meier curves were used to identify and compare risk factors and overall survival (OS).

A total of 48 patients were enrolled in the study, with an objective response rate (ORR) of 31.3%, a disease control rate (DCR) of 66.7%; the incidence of adverse events was mostly mild. A significant decrease in HBV DNA and HBsAg levels was observed at 12 and 24 weeks compared with the baseline (p < 0.05). Compared to patients with progressive disease (PD), patients with disease control showed a more significant decrease in HBV DNA and HBsAg levels at 12 and 24 weeks (p < 0.001). Eleven patients showed elevations in HBV DNA level and one of them showed HBV reactivation; however, the reactivation was not associated hepatitis. Moreover, eight patients showed elevation in HBsAg. Elevation in HBV DNA level was associated with poor tumor response (P=0.001, OR=18.643 [95% CI: 3.271–106.253]). Cox survival analysis suggested that HBV DNA increase (P=0.011, HR=4.816, 95% CI: 1.439–16.117) and HBsAg increase (P=0.022, HR=4.161, 95% CI: 1.224–16.144) were independent risk factors associated with survival time. Kaplan–Meier curves suggested that patients who exhibited an increase in HBV DNA (6.87 months vs undefined, log-rank test: p= 0.004) and HBsAg (8.07 months vs undefined, log-rank test: p= 0.004) levels had a shorter median survival time (MST). Patients without increased HBsAg showed better baseline liver function and routine blood tests (p<0.05) than patients with increased HBsAg. An increase in C-reactive protein (CRP) and interleukin-6 (IL-6), and a decrease in T lymphocytes, CD4+ T lymphocytes, and B lymphocytes at 1-week post-treatment associated with HBsAg well-controlled.

HBV-related liver cancer patients treated with combination therapy showed improved efficacy and safety profiles. Combination therapy has some effect on HBV infection, and a correlation between tumor response and antiviral efficacy was found. Elevation of HBV DNA and HBsAg levels may indicate poorer tumor response and survival time. Better baseline liver function and early immune activation may be associated with decline in HBsAg levels.

• C-reactive protein
• HBV reactivation
• hepatitis B surface antigen
• hepatitis B virus
• interleukin-6
• median survival time

Ropeginterferon alfa-2b is a novel mono-pegylated and extra-long-acting interferon, being developed for the treatment of myeloproliferative neoplasm (MPN) and chronic viral hepatitis. It has a favorable pharmacokinetic profile and less frequent dosing schedule, i.e., once every two to four weeks, compared to conventional pegylated interferon products, which have multiple isomers and are administered weekly. It was approved for the long-term treatment of polycythemia vera, an MPN, and has been included in the NCCN clinical practice guidelines for this indication. Ropeginterferon alfa-2b has demonstrated efficacy and showed a favorable safety profile for the treatment of chronic viral hepatitis in several clinical studies. In this article, we review its pharmacokinetics and available clinical data and suggest that ropeginterferon alfa-2b administered once every two weeks can serve as a new treatment option for patients with chronic viral hepatitis, including chronic hepatitis B, C, and D.

Despite the availability of effective vaccination, hepatitis B virus (HBV) infection continues to be a major challenge worldwide. Research efforts are ongoing to find an effective cure for the estimated 250 million people chronically infected by HBV in recent years. The exceptionally limited host spectrum of HBV has limited the research progress. Thus, different HBV mouse models have been developed and used for studies on infection, immune responses, pathogenesis, and antiviral therapies. However, these mouse models have great limitations as no spread of HBV infection occurs in the mouse liver and no or only very mild hepatitis is present. Thus, the suitability of these mouse models for a given issue and the interpretation of the results need to be critically assessed. This review summarizes the currently available mouse models for HBV research, including hydrodynamic injection, viral vector-mediated transfection, recombinant covalently closed circular DNA (rc-cccDNA), transgenic, and liver humanized mouse models. We systematically discuss the characteristics of each model, with the main focus on hydrodynamic injection mouse model. The usefulness and limitations of each mouse model are discussed based on the published studies. This review summarizes the facts for considerations of the use and suitability of mouse model in future HBV studies.

• hepatitis B virus
• hydrodynamic injection
• liver humanized mouse
• transgenic mouse
• viral vector

Hepatitis B virus (HBV)-related liver cirrhosis (LC) complicated with severe sepsis (SS) leads to HBV-related acute-on-chronic liver failure (HBV-ACLF). Programmed cell death ligand-1 (PD-L1)-associated immunosuppression is involved in both LC and SS. This study aimed to examine the expression and clinical relevance of PD-L1 on peripheral CD14+ monocytes in sepsis-induced HBV-ACLF.

PD-L1 expression on peripheral CD14+ monocytes among the healthy control (HC), LC and LC + SS groups was examined using flow cytometry analysis and compared. In the LC + SS group, an SS-induced ACLF subgroup was identified. LC + SS patients were followed up for 28 days. The correlations between monocytic PD-L1 expression and illness severity scores and the prognostic value of monocytic PD-L1 expression in SS-induced HBV-ACLF patients was examined.

There were 17, 30 and 70 participants in the HC, LC and LC + SS groups, respectively. The monocytic PD-L1 expression was higher in the LC group compared with the HC group and in the LC + SS group compared with the LC group. The monocytic PD-L1 expression was positively correlated with the illness severity scores in LC + SS patients and predicted 28-day mortality of SS-induced HBV-ACLF patients (n = 59).

Severe sepsis exhibits a superimposed effect of monocytic PD-L1 up-regulation on the basis of liver cirrhosis, and monocytic PD-L1 expression predicts 28-day mortality of SS-induced HBV-ACLF.

• ACLF
• PD-L1
• immunosuppression
• liver cirrhosis
• sepsis

• Head and neck cancer carcinoma
• Hepatocellular carcinoma
• Hodgkin lymphoma
• Immune checkpoint inhibitors
• Non-hodgkin lymphoma
• Non-small cell lung cancer
• Renal cell carcinoma

• Chagas disease
• Trypanosoma cruzi infection
• hepatic immune response
• liver

• hepatitis B virus
• immune checkpoint inhibitors
• immunotherapy
• reactivation

• Adult
• Aged
• Aged, 80 and over
• B7-H1 Antigen/metabolism
• Female
• Hepatitis B virus/drug effects
• Humans
• Immune Checkpoint Inhibitors/adverse effects
• Immune Checkpoint Inhibitors/metabolism
• Immune Checkpoint Inhibitors/therapeutic use
• Male
• Middle Aged
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Programmed Cell Death 1 Receptor/metabolism
• Retrospective Studies

• Dendritic cells
• Hepatocellular carcinoma
• ILT4
• Immune tolerance

• Baicalin
• HBV
• HNF1α
• HNF4α
• transactivation

• Hepatitis B virus
• Hepatitis D virus
• Hepatocyte
• Mouse
• Non-human primate
• Sodium taurocholate co-transporting polypeptide

• Animals
• Disease Models, Animal
• Hepatitis B/virology
• Hepatitis B virus/pathogenicity
• Hepatitis D/virology
• Hepatitis Delta Virus/pathogenicity
• Hepatocytes/virology
• Macaca/virology
• Mice
• Virus Internalization

• R01 AI144008 NIAID NIH HHS

• hepatitis B virus
• hepatocellular carcinoma
• immunotherapy
• programmed cell death protein 1
• programmed death-ligand 1
• tumor microenvironment

Hepatitis B virus (HBV) persistently infected about 250 million people worldwide, and a curative treatment remains an unmet medical need. Among many approaches to treat chronic hepatitis B (CHB), therapeutic vaccines have been developed for two decades, but none have yielded promising results in clinical trials. Therefore, dissection of HBV clearance mechanisms during therapeutic vaccination in appropriate models, which could give rise to new curative therapies, is urgently needed. Growing evidence indicates that prolonged and intensive exposure of antigen-specific T cells to viral antigens is a major cause of T cell exhaustion, and decreases anti-HBV immunity efficacy of therapeutic vaccination. HBV X protein (HBx) is expressed at low levels, and the understanding of its immunogenicity and potential in therapeutic CHB vaccines is limited.

HBV genome sequences from CHB patients were cloned into a pAAV plasmid backbone and transfected into immunocompetent mouse hepatocytes through hydrodynamic injection. Mice carrying > 500 IU/mL serum HBV surface antigen (HBs) for more than 4 weeks were considered HBV carriers mimicking human CHB and received 3 doses of weekly HBx vaccine by subcutaneous immunization. Serum HBV clearance was evaluated by monitoring serum HBs and HBV-DNA titers. Residual HBV in the liver was evaluated by western blotting for HBV core antigen. The splenic antigen-specific T cell response was quantified by a 15-mer overlapping peptide-stimulated interferon-γ enzyme-linked immunospot assay. Blood and hepatic immune cells were quantified by flow cytometric analysis.

Our HBx-based vaccine induced systemic HBx-specific CD4⁺ and CD8⁺ T cell responses in HBV carrier mice and demonstrated significant HBs and HBV-DNA elimination. The protective effect persisted for at least 30 days without additional booster immunization. Different infiltrating myeloid cell subsets, each with distinctive roles during immune-mediated HBV clearance, were found in the liver of vaccinated mice. During vaccine therapy, inflammatory monocyte depletion resulted in sustained HBV clearance inhibition, whereas phagocytic monocyte-derived macrophage and Kupffer cell elimination resulted in only transient inhibition of vaccine-induced HBV clearance.

We report the potential role of HBx as a major immunogen in an HBV therapeutic vaccine and the significance of a liver-infiltrating monocyte subset during hepatic viral clearance.

• Chronic hepatitis B
• Hepatic innate immunity
• Immunotherapy
• Myeloid cell

Many pathogens use the same immune evasion mechanisms as cancer cells. Patients with chronic infections have elevated levels of checkpoint receptors (e.g., programed cell death 1, PD1) on T cells. Monoclonal antibody (mAb)-based inhibitors to checkpoint receptors have also been shown to enhance T-cell responses in models of chronic infection. Therefore, inhibitors have the potential to act as a vaccine “adjuvant” by facilitating the expansion of vaccine antigen-specific T-cell repertoires. Here, we report the discovery and characterization of a peptide-based class of PD1 checkpoint inhibitors, which have a potent adaptive immunity adjuvant capability for vaccines against infectious diseases. Briefly, after identifying peptides that bind to the recombinant human PD1, we screened for in vitro efficacy in reporter assays and human peripheral blood mononuclear cells (PBMC) readouts. We first found the baseline in vivo performance of the peptides in a standard mouse oncology model that demonstrated equivalent efficacy compared to mAbs against the PD1 checkpoint. Subsequently, two strategies were used to demonstrate the utility of our peptides in infectious disease indications: (1) as a therapeutic in a bacteria-induced lethal sepsis model in which our peptides were found to increase survival with enhanced bacterial clearance and increased macrophage function; and (2) as an adjuvant in combination with a prophylactic malaria vaccine in which our peptides increased T-cell immunogenicity and the protective efficacy of the vaccine. Therefore, our peptides are promising as both a therapeutic agent and a vaccine adjuvant for infectious disease with a potentially safer and more cost-effective target product profile compared to mAbs. These findings are essential for deploying a new immunomodulatory regimen in infectious disease primary and clinical care settings.

• T-cell
• adjuvant
• cancer
• checkpoint
• malaria
• peptides
• sepsis
• vaccine

Treatment of chronic hepatitis B virus (HBV) infection is highly effective in suppressing viral replication, but complete cure is rarely achieved. In recent years, substantial progress has been made in the development of immunotherapy to treat cancer. Applying these therapies to improve the management of chronic HBV infection is now being attempted, and has become an area of active research. Immunotherapy with vaccines and checkpoint inhibitors can boost T cell functions in vitro, and therefore may be used to reinvigorate the impaired HBV-specific T cell response. However, whether these approaches will suffice and restore antiviral T cell immunity to induce long-term HBV control remains an open question. Recent efforts have begun to describe the phenotype and function of HBV-specific T cells on the single epitope level. An improved understanding of differing T cell specificities and their contribution to HBV control will be instrumental for advancement of the field. In this review, we outline correlates of successful versus inadequate T cell responses to HBV, and discuss the rationale behind therapeutic vaccines and checkpoint inhibitors for the treatment of chronic HBV infection.

• HBV-specific T cells
• checkpoint inhibitors
• hepatitis B virus
• immunotherapy
• therapeutic vaccines

• HBV clearance
• asialo GM-1
• liver-resident CD8 T cells

• Functional cure
• Hepatitis delta virus
• Hepatitis B virus
• Nucleos(t)ide analogues
• Peginterferon alfa-2a

• Antiviral Agents/therapeutic use
• Hepatitis B Surface Antigens
• Hepatitis B virus/drug effects
• Hepatitis B virus/isolation & purification
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/virology
• Hepatitis D/drug therapy
• Hepatitis D/virology
• Hepatitis Delta Virus/drug effects
• Hepatitis Delta Virus/isolation & purification
• Humans
• Interferon-alpha/adverse effects
• Interferon-alpha/therapeutic use
• Nucleosides/adverse effects
• Nucleosides/therapeutic use
• Nucleotides/adverse effects
• Nucleotides/therapeutic use

• Cirrhosis
• Hepatitis
• Telomere

• antiviral therapy
• children
• chronic hepatitis B
• hepatitis B vaccination
• pediatric hepatitis B
• pregnant women
• universal infant immunization

• Hepatitis B virus vaccine
• hepatitis immunity
• immunologic response

• Norepinephrine
• Programmed cell death-1
• Sympathetic nervous system
• T cell dysfunction
• Traumatic brain injury

• Adrenergic beta-Antagonists/pharmacology
• Animals
• Brain Contusion/immunology
• Brain Injuries, Traumatic/immunology
• CD4-Positive T-Lymphocytes/drug effects
• CD4-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/drug effects
• CD8-Positive T-Lymphocytes/immunology
• Flow Cytometry
• Immune Tolerance/immunology
• Interferon-gamma/immunology
• Leukocytes, Mononuclear/immunology
• Norepinephrine/metabolism
• Programmed Cell Death 1 Receptor/drug effects
• Programmed Cell Death 1 Receptor/immunology
• Propranolol/pharmacology
• Rats
• Sympathetic Nervous System/drug effects
• Sympathetic Nervous System/immunology
• Tumor Necrosis Factor-alpha/immunology
• Up-Regulation

Trypanosoma cruzi infection is characterized by chronic parasitism of non-lymphoid tissues and is rarely eliminated despite potent adaptive immune responses. This failure to cure has frequently been attributed to a loss or impairment of anti-T. cruzi T cell responses over time, analogous to the T cell dysfunction described for other persistent infections. In this study, we have evaluated the role of CD8⁺ T cells during chronic T. cruzi infection (>100 dpi), with a focus on sites of pathogen persistence. Consistent with repetitive antigen exposure during chronic infection, parasite-specific CD8⁺ T cells from multiple organs expressed high levels of KLRG1, but exhibit a preferential accumulation of CD69⁺ cells in skeletal muscle, indicating recent antigen encounter in a niche for T. cruzi persistence. A significant proportion of CD8⁺ T cells in the muscle also produced IFNγ, TNFα and granzyme B in situ, an indication of their detection of and functional response to T. cruzi in vivo. CD8⁺ T cell function was crucial for the control of parasite burden during chronic infection as exacerbation of parasite load was observed upon depletion of this population. Attempts to improve T cell function by blocking PD-1 or IL-10, potential negative regulators of T cells, failed to increase IFNγ and TNFα production or to enhance T. cruzi clearance. These results highlight the capacity of the CD8⁺ T cell population to retain essential in vivo function despite chronic antigen stimulation and support a model in which CD8⁺ T cell dysfunction plays a negligible role in the ability of Trypanosoma cruzi to persist in mice.

The parasite Trypanosoma cruzi establishes lifelong infections in humans and other mammals, leading to severe cardiac and gastrointestinal complications known as Chagas disease. Although the factors that enable T. cruzi persistence remain undefined, in this and many other infection models, pathogen persistence has been attributed to the exhaustion of the immune system, particularly of CD8⁺ T cells. Here, we show that the inability of hosts to fully resolve T. cruzi infection is not a result of immune exhaustion and that in fact the T. cruzi-specific CD8⁺ T cell population remains highly competent and actively suppresses parasite outgrowth throughout the chronic infection. These results demonstrate that compromised immunity is not the eventual outcome of all chronic infections and suggest that T. cruzi, and perhaps other pathogens, may employ alternative strategies to subvert immune clearance in the presence of highly functional pathogen-specific effectors. These findings also suggest that interventions to inhibit immune regulatory pathways or to otherwise boost existing immune responses in such infections, will have limited benefit.

• Animals
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/metabolism
• CD8-Positive T-Lymphocytes/physiology
• Chagas Disease/immunology
• Chagas Disease/metabolism
• Lectins, C-Type/genetics
• Lectins, C-Type/metabolism
• Longitudinal Studies
• Mice
• Mice, Inbred C57BL
• Muscle, Skeletal/immunology
• Receptors, Immunologic
• Trans-Activators/genetics
• Trans-Activators/metabolism
• Trypanosoma cruzi/immunology
• Trypanosoma cruzi/pathogenicity
• Tumor Necrosis Factor-alpha

• T32 AI007511 NIAID NIH HHS
• R01 AI124692 NIAID NIH HHS
• T32 AI060546 NIAID NIH HHS
• R01 AI089952 NIAID NIH HHS
• National Institutes of Health (US)
• national institutes of health

• Cancer
• HIV
• Hepatitis B
• Hepatitis C
• Immunotherapy
• Organ transplant
• PD-1

• Aged
• Antineoplastic Agents, Immunological/adverse effects
• Antineoplastic Agents, Immunological/therapeutic use
• B7-H1 Antigen/antagonists & inhibitors
• Female
• Graft Rejection/etiology
• HIV Infections/complications
• Hepatitis B, Chronic/complications
• Hepatitis C, Chronic/complications
• Humans
• Immunotherapy/adverse effects
• Male
• Melanoma/complications
• Melanoma/drug therapy
• Middle Aged
• Molecular Targeted Therapy/adverse effects
• Neoplasm Proteins/antagonists & inhibitors
• Neoplasms/complications
• Neoplasms/drug therapy
• Postoperative Complications/drug therapy
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Retrospective Studies
• Transplant Recipients
• Treatment Outcome

• 18176 Cancer Research UK
• K12 CA090625 NCI NIH HHS

Tuberculosis (TB) has tremendous public health relevance. It most frequently affects the lung and is characterized by the development of unique tissue lesions, termed granulomas. These lesions encompass various immune populations, with macrophages being most extensively investigated. Myeloid derived suppressor cells (MDSCs) have been recently identified in TB patients, both in the circulation and at the site of infection, however their interactions with Mycobacterium tuberculosis (Mtb) and their impact on granulomas remain undefined. We generated human monocytic MDSCs and observed that their suppressive capacities are retained upon Mtb infection. We employed an in vitro granuloma model, which mimics human TB lesions to some extent, with the aim of analyzing the roles of MDSCs within granulomas. MDSCs altered the structure of and affected bacterial containment within granuloma-like structures. These effects were partly controlled through highly abundant secreted IL-10. Compared to macrophages, MDSCs activated primarily the NF-κB and MAPK pathways and the latter largely contributed to the release of IL-10 and replication of bacteria within in vitro generated granulomas. Moreover, MDSCs upregulated PD-L1 and suppressed proliferation of lymphocytes, albeit with negligible effects on Mtb replication. Further comprehensive characterization of MDSCs in TB will contribute to a better understanding of disease pathogenesis and facilitate the design of novel immune-based interventions for this deadly infection.

• IL-10
• Mycobacterium tuberculosis
• PD-L1
• granuloma
• myeloid-derived suppressor cells
• tuberculosis

Novel compounds and more efficient treatment options are urgently needed for the treatment of cystic echinococcosis (CE), which is caused by Echinococcus granulosus. The decoction of Sophora moorcroftiana (Fabaceae) has been used to treat parasitosis for years in traditional Tibetan medicine. The aim of this study was to screen insecticidal water-soluble alkaloids from S. moorcroftiana seeds and evaluate the therapeutic effects against CE and the immune response induced by the alkaloidal fraction. Low polarity compounds (E2-a) were isolated from water-soluble alkaloid (E2) and matrine and sophocarpine were identified as major components. The E2-a fraction was more effective against protoscoleces than other constituents from S. moorcroftiana. After 20 weeks of secondary infection with protoscoleces, mice were orally treated with E2-a (100 mg/kg/day) for 6 weeks to evaluate therapeutic and immunoregulatory activities. Compared with the untreated group, E2-a treatment induced a significant reduction in cyst weight (mean 2.93 g) (p < 0.05) and an impaired ultrastructural modification of the cyst. Interestingly, the application of E2-a resulted in a significant increased frequency of CD3⁺CD4⁺ T-cell subsets and decreased frequency of CD3⁺PD-1⁺ T-cell subsets, compared with protoscolece-infected mice without treatment. The E2-a fraction of S. moorcroftiana can inhibit the cyst development of CE and boost the specific immune response by reducing the expression of PD-1 and accelerate the cytokine secretion of antigen-specific T-cells. All data suggest the E2-a fraction from S. moorcroftiana seeds may be used as a new potential therapeutic option against E. granulosus infection.

• PD-1 polymorphism
• chronic hepatitis B virus infection
• programmed cell death-1
• spontaneous clearance

• HBV
• Immunotherapy
• anti-PD-1
• anti-PD-L1
• viral hepatitis

• CTLA-4
• PD-1
• hepatocellular carcinoma
• immune checkpoint inhibitors
• immunotherapy