Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion

Salinas, Eduardo; Boisvert, Maude; Upadhyay, Amit A.; Bédard, Nathalie; Nelson, Sydney; Bruneau, Julie; Derdeyn, Cynthia A.; Marcotrigiano, Joseph; Evans, Matthew J.; Bosinger, Steven E.; Shoukry, Naglaa H.; Grakoui, Arash

doi:10.1172/jci140590

Cited by 19 publications

(35 citation statements)

References 57 publications

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“…Studies have shown that antibody-based passive immunity plays an important role in protecting humans against pathogens such as Streptococcus pneumoniae 24 and hepatitis C virus infections. 25 At the same time, mAbs can exhibit good therapeutic effects in immunosuppressed patients. 26 Using mAbs in combination with antibiotics can mediate significant protective effects even at subinhibitory concentrations and alleviate the emergence of bacterial drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic Combined with Epitope-Specific Monoclonal Antibody Cocktail Protects Mice Against Bacteremia and Acute Pneumonia from Methicillin-Resistant Staphylococcus aureus Infection

Duan

Zhang

Chen

et al. 2021

JIR

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We previously reported that monoclonal antibody (mAb) cocktail improves survival in Staphylococcus aureus infection. In this study, we used acute pneumonia model and lethal sepsis model to investigate the efficacy of antibiotic combined with epitopespecific mAb cocktail in treating MRSA252 infection. Methods: MRSA252 was challenged by tail vein injection or tracheal intubation to establish sepsis model or pneumonia model. One hour after infection, the mice received a single intravenous injection of normal saline, vancomycin, and vancomycin combined monoclonal antibody, linezolid alone or linezolid combined monoclonal antibody. Daily record survival rate (total 7 days), bacterial load, histology, cytokine analysis of serum and alveolar lavage fluid, and in vitro determination of the neutralizing ability of antibodies to SEB toxin and Hla toxin explained the mechanism of antibody action. Results: The mAb cocktail combined with low doses of vancomycin or linezolid improved survival rates in acute pneumonia model (70%, 80%) and lethal sepsis model (80%, 80%). Epitopespecific monoclonal antibodies reduced bacterial colonization in the kidneys and lungs of mice and inhibited the biological functions of the toxins Hla and SEB in vitro. Compared to the antibiotic alone or PBS groups, the combination group had higher levels of IL-1α, IL-1β and IFN-γ and lower levels of IL-6, IL-10, TNF-α. Further, the combination of antibiotic and mAb cocktail improved infection survival against the clinical MRSA isolates in a lethal sepsis model. Conclusion:This study demonstrates a novel method to treat people with low immunity against drug-resistant S. aureus infections.

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Section: Discussionmentioning

confidence: 99%

Antibiotic Combined with Epitope-Specific Monoclonal Antibody Cocktail Protects Mice Against Bacteremia and Acute Pneumonia from Methicillin-Resistant Staphylococcus aureus Infection

Duan

Zhang

Chen

et al. 2021

JIR

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“…Development of neutralizing Abs (NAbs) is generally delayed during acute infection ( 55 – 57 ). Although Ab responses are short lived in resolvers ( 58 ), they appeared early during acute resolving infection(s) in some subjects following expansion of activated circulating T follicular helper cells (cTfh) expressing IL-21 that help expansion of HCV-specific B cells ( 59 ). Generation of NAbs correlated with spontaneous resolution in other studies ( 17 , 60 ).…”

Section: Hcv Monoinfectionmentioning

confidence: 99%

“…CD4 + helper T cells are also essential for optimal B cell function and production of neutralizing antibodies. Specifically, antigen-specific B cell affinity maturation, isotype class switching and differentiation into antibody-secreting plasma cells in germinal centers are regulated by direct contact with CD4 + Tfh cells ( 59 , 149 ).…”

Section: Hcv/hiv Co-infectionmentioning

confidence: 99%

A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection

2021

Self Cite

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Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.

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“…Examining peripherally circulating Tfh cells instead of the Tfh cells in lymphoid tissues in patients with acute HCV infection, the number correlates with the amount of anti-HCV antibody, and when HCV is removed by anti-HCV drug treatment, the number of peripheral Tfh cells increases [130,131]. Salinas et al reported that in HCV patients who heal spontaneously, peripheral Tfh cells that produce IL-21 appear early in infection, followed by anti-HCV E2 glycoprotein-specific antibodies [132].…”

Section: Hcv Infectionmentioning

confidence: 99%

Interleukin-21 in Viral Infections

Asao

2021

IJMS

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Interleukin (IL)-21 is a cytokine that affects the differentiation and function of lymphoid and myeloid cells and regulates both innate and adaptive immune responses. In addition to regulating the immune response to tumor and viral infections, IL-21 also has a profound effect on the development of autoimmune and inflammatory diseases. IL-21 is produced mainly from CD4+ T cells—in particular, follicular helper T (Tfh) cells—which have a great influence on the regulation of antibody production. It is also an important cytokine for the activation of CD8+ T cells, and its role in recovering the function of CD8+ T cells exhausted by chronic microbial infections and cancer has been clarified. Thus, IL-21 plays an extremely important role in viral infections, especially chronic viral infections. In this review, I will introduce the findings to date on how IL-21 is involved in some typical viral infections and the potential of treating viral diseases with IL-21.

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Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion

Cited by 19 publications

References 57 publications

Antibiotic Combined with Epitope-Specific Monoclonal Antibody Cocktail Protects Mice Against Bacteremia and Acute Pneumonia from Methicillin-Resistant Staphylococcus aureus Infection

Antibiotic Combined with Epitope-Specific Monoclonal Antibody Cocktail Protects Mice Against Bacteremia and Acute Pneumonia from Methicillin-Resistant Staphylococcus aureus Infection

A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection

Interleukin-21 in Viral Infections

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