Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance

Nat Commun. 2015 May 19:6:7090. doi: 10.1038/ncomms8090.

Abstract

Unrelenting environmental challenges to the gut epithelium place particular demands on the local immune system. In this context, intestinal intraepithelial lymphocytes (IEL) compose a large, highly conserved T cell compartment, hypothesized to provide a first line of defence via cytolysis of dysregulated intestinal epithelial cells (IEC) and cytokine-mediated re-growth of healthy IEC. Here we show that one of the most conspicuous impacts of activated IEL on IEC is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. Indeed, IEL activation in vivo rapidly provoked type I/III IFN receptor-dependent upregulation of IFN-responsive genes in the villus epithelium. Consistent with this, activated IEL mediators protected cells against virus infection in vitro, and pre-activation of IEL in vivo profoundly limited norovirus infection. Hence, intraepithelial T cell activation offers an overt means to promote the innate antiviral potential of the intestinal epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caliciviridae Infections / immunology*
  • Cytokines / metabolism
  • Epithelial Cells / immunology
  • Female
  • Gastroenteritis / immunology*
  • Gastroenteritis / virology
  • Immunity, Innate
  • Interferon-alpha / metabolism
  • Interferon-gamma / metabolism
  • Interferons / metabolism
  • Intestine, Small / metabolism
  • Lymphocyte Activation*
  • Lymphocytes / immunology
  • Macrophages / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Norovirus / immunology*
  • T-Lymphocytes / immunology

Substances

  • Cytokines
  • Interferon-alpha
  • Interferon-gamma
  • Interferons

Associated data

  • GEO/GSE63364