NK1.1+ cells are required for neutrophil recruitment to sites of early viral infection (43.4)

Abstract

Abstract LCMV replication is controlled by type I and II interferon (IFN) responses that drive antigen specific T cell expansion and function. It is unclear whether innate immune cells contribute to the initiation of T cell responses. We focused on two innate cell populations, natural killer (NK) cells and CD11b+ cells (Ly6G+ Ly6C+ neutrophils and Ly6G- Ly6C+ monocytes), hypothesizing that sensing of LCMV infection in the spleen drives recruitment of innate cell populations to sites of early infection. C57BL/6-WT or IFN-αR1, IFN-γR, MyD88 or MAVS deficient mice were infected with 2x106 PFU LCMV-Armstrong. Mice were sacrificed at 14, 24, 72 hrs post infection (pi) at which time neutrophil and NK cell recruitment to LCMV infected cells in the spleen was determined by immunofluorescence staining. In WT mice, neutrophils and NK cells were recruited to sites of infection as early as 14 hrs, but dissipated by 72 hrs pi. Depletion of NK1.1+ cells prior to infection abrogated neutrophil recruitment at 24 hrs pi. Furthermore, recruitment of neutrophils to sites of infection was fully dependent on MyD88 and partially dependent on MAVS, but was independent of type I or II IFN receptors. To conclude, our data demonstrate that neutrophil recruitment to sites of early LCMV infection is completely dependent on NK cells and MyD88 signaling, partially dependent on MAVS signaling, and independent of IFN responses. Supported by Arthritis Foundation