Interleukin-17A Promotes CD8 ⁺ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance

Abstract

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.