ILC1 Confer Early Host Protection at Initial Sites of Viral Infection

Orr El Weizman, Nicholas M. Adams, Iona S. Schuster, Chirag Krishna, Yuri Pritykin, Colleen Lau, Mariapia A. Degli-Esposti, Christina S. Leslie, Joseph C. Sun, Timothy E. O'Sullivan

Research output: Contribution to journalArticleResearchpeer-review

182 Citations (Scopus)

Abstract

Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Whether tissue-resident lymphocytes confer early antiviral immunity at local sites of primary infection prior to the initiation of circulating responses is not well understood. Furthermore, the kinetics of initial antiviral responses at sites of infection remain unclear. Here, we show that tissue-resident type 1 innate lymphoid cells (ILC1) serve an essential early role in host immunity through rapid production of interferon (IFN)-γ following viral infection. Ablation of Zfp683-dependent liver ILC1 lead to increased viral load in the presence of intact adaptive and innate immune cells critical for mouse cytomegalovirus (MCMV) clearance. Swift production of interleukin (IL)-12 by tissue-resident XCR1+ conventional dendritic cells (cDC1) promoted ILC1 production of IFN-γ in a STAT4-dependent manner to limit early viral burden. Thus, ILC1 contribute an essential role in viral immunosurveillance at sites of initial infection in response to local cDC1-derived proinflammatory cytokines. Innate lymphoid cells have a non-redundant role as initial responders to viral infections.

Original languageEnglish
Pages (from-to)795-808
Number of pages14
JournalCell
Volume171
Issue number4
DOIs
Publication statusPublished - 2 Nov 2017
Externally publishedYes

Keywords

  • cDC1
  • ILC1
  • infection
  • influenza
  • innate immunity
  • MCMV
  • sendai virus
  • tissue-resident

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