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Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance

Author

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  • Mahima Swamy

    (Immunosurveillance lab, Francis Crick Institute
    King’s College London, Borough Wing, Guy’s Hospital, Great Maze Pond
    Cell Signalling and Immunology, College of Life Sciences, University of Dundee)

  • Lucie Abeler-Dörner

    (Immunosurveillance lab, Francis Crick Institute
    King’s College London, Borough Wing, Guy’s Hospital, Great Maze Pond)

  • James Chettle

    (University of Cambridge)

  • Tanel Mahlakõiv

    (Institute of Virology, University Medical Center
    Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg)

  • Delphine Goubau

    (Immunosurveillance lab, Francis Crick Institute)

  • Probir Chakravarty

    (Immunosurveillance lab, Francis Crick Institute)

  • George Ramsay

    (Cell Signalling and Immunology, College of Life Sciences, University of Dundee)

  • Caetano Reis e Sousa

    (Immunosurveillance lab, Francis Crick Institute)

  • Peter Staeheli

    (Institute of Virology, University Medical Center)

  • Barbara A. Blacklaws

    (University of Cambridge)

  • Jonathan L. Heeney

    (University of Cambridge)

  • Adrian C. Hayday

    (Immunosurveillance lab, Francis Crick Institute
    King’s College London, Borough Wing, Guy’s Hospital, Great Maze Pond)

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.

Suggested Citation

  • 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., 2015. "Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8090
    DOI: 10.1038/ncomms8090
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    Cited by:

    1. Tao Yang & Tian Li & Yingying Xing & Mengtao Cao & Mingxiang Zhang & Qibin Leng & Ju Qiu & Xinyang Song & Jianfeng Chen & Guohong Hu & Youcun Qian, 2024. "Dietary nucleic acids promote oral tolerance through innate sensing pathways in mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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