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

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

Author information

1
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA, USA.
2
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
3
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA, USA. mgale@uw.edu.

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.

PMID:
31235953
PMCID:
PMC6642690
[Available on 2019-12-24]
DOI:
10.1038/s41590-019-0408-z
[Indexed for MEDLINE]

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