Interferon-? modulates dendritic cells to facilitate T cell immunity during infection with influenza A virus.

ABSTRACT: Type III interferon (IFN-?) is important for innate immune protection at mucosal surfaces and has therapeutic benefit against influenza A virus (IAV) infection. However, the mechanisms by which IFN-? programs adaptive immune protection against IAV are undefined. Here we found that IFN-? signaling in dendritic cell (DC) populations was critical for the development of protective IAV-specific CD8+ T cell responses. Mice lacking the IFN-? receptor (Ifnlr1-/-) had blunted CD8+ T cell responses relative to wild type and exhibited reduced survival after heterosubtypic IAV re-challenge. Analysis of DCs revealed IFN-? signaling directed the migration and function of CD103+ DCs for development of optimal antiviral CD8+ T cell responses, and bioinformatic analyses identified IFN-? regulation of a DC IL-10 immunoregulatory network. Thus, IFN-? serves a critical role in bridging innate and adaptive immunity from lung mucosa to lymph nodes to program DCs to direct effective T cell immunity against IAV.

SUBMITTER: Hemann EA 

PROVIDER: S-EPMC6642690 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature