Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance.
Dhiraj Acharya,Penghua Wang,Penghua Wang,Amber M. Paul,Jianfeng Dai,Jianfeng Dai,David Gate,Jordan E. Lowery,Dobrivoje S. Stokic,A. Arturo Leis,Richard A. Flavell,Terrence Town,Erol Fikrig,Fengwei Bai +13 more
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TLDR
It is demonstrated that IL-17A protects mice from lethal WNV infection by promoting CD8+ T cell-mediated clearance of WNV and may have broad implications for immunity to other microbial infections and cancers, where CD8- T cell functions are crucial.Abstract:
CD8 + T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 + T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient ( Il17a −/− ) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 + T cells isolated from Il17a −/− mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo . Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A. In conclusion, we report a novel function of IL-17A in promoting CD8 + T cell cytotoxicity, which may have broad implications in other microbial infections and cancers. IMPORTANCE Interleukin-17A (IL-17A) and CD8 + T cells regulate diverse immune functions in microbial infections, malignancies, and autoimmune diseases. IL-17A is a proinflammatory cytokine produced by diverse cell types, while CD8 + T cells (known as cytotoxic T cells) are major cells that provide immunity against intracellular pathogens. Previous studies have demonstrated a crucial role of CD8 + T cells in recovery from West Nile virus (WNV) infection. However, the role of IL-17A during WNV infection remains unclear. Here, we demonstrate that IL-17A protects mice from lethal WNV infection by promoting CD8 + T cell-mediated clearance of WNV. In addition, treatment of WNV-infected mice with recombinant IL-17A reduces the viral burden and increases survival of mice, suggesting a potential therapeutic. This novel IL-17A–CD8 + T cell axis may also have broad implications for immunity to other microbial infections and cancers, where CD8 + T cell functions are crucial.read more
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Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4 + T Cells in COVID-19.
Benjamin J Meckiff,Ciro Ramírez-Suástegui,Vicente Fajardo,Serena J Chee,Anthony Kusnadi,Hayley Simon,Simon Eschweiler,Alba Grifoni,Emanuela Pelosi,Daniela Weiskopf,Alessandro Sette,Alessandro Sette,Ferhat Ay,Grégory Seumois,Christian H. Ottensmeier,Christian H. Ottensmeier,Christian H. Ottensmeier,Pandurangan Vijayanand,Pandurangan Vijayanand,Pandurangan Vijayanand +19 more
TL;DR: In hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness which correlated negatively with antibody levels to SARS-CoV-2 spike protein, and these analyses provide insights into the gene expression patterns of Sars-Cov-2-reactive CD4+ T cells in distinct disease severities.
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The protective and pathogenic roles of IL-17 in viral infections: friend or foe?
TL;DR: Accumulated experimental and clinical evidence has broadened the understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL- 17-targeted immunotherapy may be a promising therapeutic option.
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Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice.
Maria Daglas,Dominik F. Draxler,Heidi Ho,Fiona McCutcheon,Adam Galle,Amanda E. Au,Pia Larsson,Julia L. Gregory,Frank Alderuccio,Maithili Sashindranath,Robert L. Medcalf +10 more
TL;DR: Using a TBI mouse model, changes in the local immune response with neurodegeneration/neurological dysfunction over an 8-month period are correlated, indicating a persistent detrimental role for cytotoxic T cells post-TBI.
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Herpes Simplex Virus Cell Entry Mechanisms: An Update.
TL;DR: In this article, the authors have discussed viral entry mechanisms including the pH-independent as well as pH-dependent endocytic entry, cell to cell spread of HSV and use of viral glycoproteins as an antiviral target.
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Single-Cell Transcriptomic Analysis of SARS-CoV-2 Reactive CD4 + T Cells
Benjamin J Meckiff,Ciro Ramírez-Suástegui,Vicente Fajardo,Serena J Chee,Anthony Kusnadi,Hayley Simon,Alba Grifoni,Emanuela Pelosi,Daniela Weiskopf,Alessandro Sette,Alessandro Sette,Ferhat Ay,Grégory Seumois,Christian H. Ottensmeier,Pandurangan Vijayanand +14 more
TL;DR: Large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 32 COVID-19 patients provides so far unprecedented insights into the gene expression patterns of SARS-CoV-2 reactive CD4- T cells in distinct disease severities.
References
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Heon Park,Zhaoxia Li,Xuexian O. Yang,Seon Hee Chang,Roza Nurieva,Yi Hong Wang,Ying Wang,Leroy Hood,Zhou Zhu,Qiang Tian,Chen Dong +10 more
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Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17
TL;DR: Evidence is presented that murine IL-23, which is produced by activated dendritic cells, acts on memory T cells, resulting in elevated IL-17 secretion, which suggests that during a secondary immune response, IL- 23 can promote an activation state with features distinct from the well characterized Th1 and Th2 profiles.
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Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense
Peng Ye,Fred H. Rodriguez,Suzanne T. Kanaly,Kim L. Stocking,Jill R. Schurr,Paul Schwarzenberger,Peter Oliver,Weitao Huang,Ping Zhang,Jason Zhang,Judd E. Shellito,G. J. Bagby,Steve Nelson,Keith Charrier,Jacques J. Peschon,Jay K. Kolls +15 more
TL;DR: Impaired IL-17R signaling is supported as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.
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Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation.
Hania Kebir,Katharina Kreymborg,Igal Ifergan,Aurore Dodelet-Devillers,Romain Cayrol,Monique Bernard,Fabrizio Giuliani,Nathalie Arbour,Burkhard Becher,Alexandre Prat +9 more
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