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Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development

Author

Listed:
  • Edwin Leeansyah

    (Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge)

  • Liyen Loh

    (University of California San Francisco
    Present address: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia)

  • Douglas F. Nixon

    (University of California San Francisco)

  • Johan K. Sandberg

    (Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge)

Abstract

Innate-like, evolutionarily conserved MR1-restricted mucosa-associated invariant T (MAIT) cells represent a large antimicrobial T-cell subset in humans. Here, we investigate the development of these cells in second trimester human fetal tissues. MAIT cells are rare and immature in the fetal thymus, spleen and mesenteric lymph nodes. In contrast, mature IL-18Rα+ CD8αα MAIT cells are enriched in the fetal small intestine, liver and lung. Independently of localization, MAIT cells express CD127 and Ki67 in vivo and readily proliferate in response to Escherichia coli in vitro. Maturation is accompanied by the gradual post-thymic acquisition of the PLZF transcription factor and the ability to produce IFNγ and IL-22 in response to bacteria in mucosa. Thus, MAIT cells acquire innate-like antimicrobial responsiveness in mucosa before exposure to environmental microbes and the commensal microflora. Establishment of this arm of immunity before birth may help protect the newborn from a range of pathogenic microbes.

Suggested Citation

  • Edwin Leeansyah & Liyen Loh & Douglas F. Nixon & Johan K. Sandberg, 2014. "Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4143
    DOI: 10.1038/ncomms4143
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