title: Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance.
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.
  
  
  OBJECTIVE
  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.
authors: Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi, USA.
authors: Dhiraj
authors: D
authors: Acharya
authors: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.|Department of Microbiology and Immunology, School of Medicine, New York Medical College, Valhalla, New York, USA.
authors: Penghua
authors: P
authors: Wang
authors: Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi, USA.
authors: Amber M
authors: AM
authors: Paul
authors: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.|Institute of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, People's Republic of China.
authors: Jianfeng
authors: J
authors: Dai
authors: Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors: David
authors: D
authors: Gate
authors: Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi, USA.
authors: Jordan E
authors: JE
authors: Lowery
authors: Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center, Jackson, Mississippi, USA.
authors: Dobrivoje S
authors: DS
authors: Stokic
authors: Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center, Jackson, Mississippi, USA.
authors: A Arturo
authors: AA
authors: Leis
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
authors: Richard A
authors: RA
authors: Flavell
authors: Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors: Terrence
authors: T
authors: Town
authors: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
authors: Erol
authors: E
authors: Fikrig
authors: Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi, USA fengwei.bai@usm.edu.
authors: Fengwei
authors: F
authors: Bai
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000821:virology; D061251:Primary Cell Culture; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D014901:West Nile Fever / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D014902:West Nile virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development
chemical_list: C098680:Il17a protein, mouse; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins
keywords: CD8 T cell; IL-17A; West Nile virus