Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance

Mahima Swamy, Lucie Abeler-Dörner, James Chettle, Tanel Mahlakõiv, Delphine Goubau, Probir Chakravarty, George Ramsay, Caetano Reis e Sousa, Peter Staeheli, Barbara A Blacklaws, Jonathan L Heeney, Adrian C Hayday

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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.

Original languageEnglish
Article number7090
Number of pages12
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 19 May 2015

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Keywords

  • Animals
  • Caliciviridae Infections
  • Cytokines
  • Epithelial Cells
  • Female
  • Gastroenteritis
  • Immunity, Innate
  • Interferon-alpha
  • Interferon-gamma
  • Interferons
  • Intestine, Small
  • Lymphocyte Activation
  • Lymphocytes
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Norovirus
  • T-Lymphocytes
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Swamy, M., Abeler-Dörner, L., Chettle, J., Mahlakõiv, T., Goubau, D., Chakravarty, P., ... Hayday, A. C. (2015). Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. Nature Communications, 6, [7090]. https://doi.org/10.1038/ncomms8090