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Antimicrobial activity of mucosal-associated invariant T cells

Nature Immunology volume 11, pages 701–708 (2010)Cite this article

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A Corrigendum to this article was published on 01 October 2010

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Abstract

Mucosal-associated invariant T lymphocytes (MAIT lymphocytes) are characterized by two evolutionarily conserved features: an invariant T cell antigen receptor (TCR) α-chain and restriction by the major histocompatibility complex (MHC)-related protein MR1. Here we show that MAIT cells were activated by cells infected with various strains of bacteria and yeast, but not cells infected with virus, in both humans and mice. This activation required cognate interaction between the invariant TCR and MR1, which can present a bacteria-derived ligand. In humans, we observed considerably fewer MAIT cells in blood from patients with bacterial infections such as tuberculosis. In the mouse, MAIT cells protected against infection by Mycobacterium abscessus or Escherichia coli. Thus, MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection.

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Figure 1: Human MAIT cells respond to bacteria-infected monocytes in an MR1-dependent manner.
Figure 2: Human MAIT cells are less abundant in the blood of bacteria-infected patients.
Figure 3: T cells from mice transgenic for the specific MAIT TCR Vα and/or Vβ chains respond to E. coli–infected APCs through MR1.
Figure 4: MAIT cell activation requires a highly conserved cognate interaction between MR1 and the TCR, as well as internalization of exogenous compounds, but is independent of the classical MHC class I and class II presentation pathways.
Figure 5: MAIT cells respond to phylogenetically diverse microbes.
Figure 6: Fibroblastic cells can induce MAIT cell activation through MR1, which can present an exogenous bacteria–derived ligand.
Figure 7: Bacteria-dependent population expansion of MAIT cells, activation at the site of infection and antibacterial function.
Figure 8: Antimycobacterial activity of MAIT cells.

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  • 13 August 2010

    In the version of this article initially published, the author Shouxiong Huang (Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA) was not included. This author should be listed as author 15 (and affiliation 8). The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank T. Hansen (Washington University in St. Louis) for anti-MR1 and cell lines overexpressing MR1; J. Cadranel (Tenon Hospital) for lung biopsies; M. Chignard (Institut Pasteur) for MyD88-deficient bone marrow; L. Alexopoulou (Centre d'Immunologie de Marseille-Luminy) for TRIF-deficient bone marrow; D. Philpott (University of Toronto) for Nod1-Nod2–deficient bone marrow; J. Tschopp (University of Lausanne) for NLRP3-ASC–deficient bone marrow; M. Albert (Institut Pasteur) for IPS-1-deficient bone marrow; the microbiology department of the Curie Institute for bacterial strains; V. Sancho-Shimizu (Faculté Necker–Institut National de la Santé et de la Recherche Médicale U550) for viruses; M. Garcia, C. Billerit, S. Boissel and I. Grandjean for managing the mouse colonies; Z. Maciorowski and A. Viguier for cell sorting; and L. Guerri, V. Soumelis and S. Amigorena for critical reading of the manuscript. Supported by Institut National de la Santé et de la Recherche Médicale, Centre d′Investigation Clinique en Biothérapie 507 Institut National de la Santé et de la Recherche Médicale and Agence National de Recherches.

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Author notes

  1. Isabelle Péguillet and Amélie Guihot: These authors contributed equally to this work.

Authors and Affiliations

  1. Département de Biologie des Tumeurs, Institut Curie, Paris, France

    Lionel Le Bourhis, Emmanuel Martin, Isabelle Péguillet, Maxime Coré, Eva Lévy, Mathilde Dusseaux, Virginie Premel, Livine Duban, Delphine Robert, Claire Soudais & Olivier Lantz

  2. Institut National de la Santé et de la Recherche Médicale U932, Paris, France

    Lionel Le Bourhis, Emmanuel Martin, Maxime Coré, Eva Lévy, Mathilde Dusseaux, Virginie Premel, Livine Duban, Claire Soudais & Olivier Lantz

  3. Centre d′Investigation Clinique en Biothérapie 507, Institut Gustave Roussy and Institut Curie, Villejuif and Paris, France.,

    Isabelle Péguillet, Delphine Robert & Olivier Lantz

  4. Université Pierre et Marie Curie, University of Paris, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 945, Hôpital Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Service des Maladies Infectieuses et Tropicales, Paris, France

    Amélie Guihot & Vanina Meyssonnier

  5. Centre National de la Recherche Scientifique, Unité Propre de Service 44, Transgenesis, Archiving and Animal Models, Institut de Transgenèse, Orléans, France

    Nathalie Froux

  6. Département de Chirurgie, Institut Curie, Paris, France

    Charlotte Ngo

  7. Unité de Virologie et Immunologie Moléculaires, Unité de Rercherche 892, Institut Scientifique de Recherche Agronomique, Domaine de Vilvert, France

    Béatrice Riteau

  8. Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA

    Shouxiong Huang

  9. Laboratoire de Microbiologie, Hôpital R. Poincaré and Equipe Associé 3647, University Versailles Saint-Quentin, Garches, France

    Martin Rottman

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Contributions

L.L.B., E.M., M.C., M.D., E.L. and C.S. did most experiments; M.R. provided M. abscessus and did M. abscessus experiments with C.S.; A.G., V.M. and C.N. provided patient samples; I.P., D.R. and V.P. analyzed patient samples; N.F. managed germ-free mice and did the reconstitution experiments with L.D. and E.M.; B.R. did in vivo influenza experiments; L.L.B., E.M., C.S. and O.L. designed experiments; and L.L.B., C.S. and O.L. wrote the manuscript.

Corresponding author

Correspondence to Olivier Lantz.

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Competing interests

O.L. is inventor of a patent describing uses for manipulating the interactions between MAIT cell TCRs and MR1. For this reason, the O.L. laboratory has received some subsidies from Innate Pharma.

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Le Bourhis, L., Martin, E., Péguillet, I. et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 11, 701–708 (2010). https://doi.org/10.1038/ni.1890

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