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

Nat Immunol. 2019 Aug;20(8):1035-1045. doi: 10.1038/s41590-019-0408-z. Epub 2019 Jun 24.

Abstract

Type III interferon (IFN-λ) 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-λ programs adaptive immune protection against IAV are undefined. Here we found that IFN-λ signaling in dendritic cell (DC) populations was critical for the development of protective IAV-specific CD8+ T cell responses. Mice lacking the IFN-λ 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-λ signaling directed the migration and function of CD103+ DCs for development of optimal antiviral CD8+ T cell responses, and bioinformatic analyses identified IFN-λ regulation of a DC IL-10 immunoregulatory network. Thus, IFN-λ 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Dendritic Cells / immunology*
  • Dogs
  • Female
  • Immunity, Innate / immunology
  • Influenza A virus / immunology*
  • Interferon gamma Receptor
  • Interferon-gamma / immunology*
  • Interleukin-10 / immunology
  • Madin Darby Canine Kidney Cells
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology*
  • Receptors, Interferon / genetics
  • Receptors, Interferon / immunology*

Substances

  • IFNG protein, mouse
  • IL10 protein, mouse
  • Receptors, Interferon
  • Interleukin-10
  • Interferon-gamma