Direct and Indirect type I Interferon signaling regulates Eomes-driven Th1-responses against Influenza Virus

Abstract In the absence of Th1 master regulator, T-box transcription factor, T-bet, CD4 T cells primed by Influenza A Virus (IAV) infection, gain Th17 attributes while still retaining robust functionality. We recently found factor Eomesodermin (Eomes), to regulate this residual identity T-bet −/−CD4 cells. However, it is unclear how Eomes regulated in cells, especially during antiviral responses. Here we find type I interferons be potent inducers but not naïve antigen specific stimulated vitro. Furthermore, blocking IFN signaling IAV infected WT host mice, reduces expression and drives functional shifts mirroring −/−Eomes −/−cells, including significantly reduced IFNγ production stronger identity. To test impact direct signals on Eomes-driven compared responses versus −/−cells also deficient for receptor. While double-deficient were compromised responding hosts treated block systemic most impacted. These results indicate a strong role indirect regulating Eomes-dependent functions Finally, depletion plasmacytoid dendritic major source IFN, does cell response. Together, these identify an important axis controlling that may future harnessed fine-tune effector memory vaccination Supported grants from NIH (R01 AI67994 R21 AI146647)