IL-22 driven neutrophils afford critical protection from acute murine cytomegalovirus infection (P6310)

Abstract

Abstract Pathogenic herpesviruses including cytomegalovirus target numerous host organs during infection, but the immunological mechanisms that afford antiviral protection in different tissue microenvironments require a better understanding. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that neutrophils are critical antiviral effector cells that counter acute herpesvirus infection. Depletion of Ly6G+ neutrophils exacerbated virus-induced weight loss and elevated virus load in a tissue-restricted manner. Neutrophils profoundly and directly inhibited virus replication in vitro. MCMV-elicited neutrophil responses were orchestrated by interleukin-22 (IL-22), which was expressed by conventional NK cells and induced neutrophil-attractant chemokines in MCMV-infected peripheral organs. These data demonstrate that IL-22 affords anti-herpesvirus infection in peripheral tissue and highlights a previously unappreciated and critical role for neutrophils in countering cytomegalovirus infection.