MAIT cells detect and efficiently lyse bacterially-infected epithelial cells

PLoS Pathog. 2013;9(10):e1003681. doi: 10.1371/journal.ppat.1003681. Epub 2013 Oct 10.

Abstract

Mucosal associated invariant T cells (MAIT) are innate T lymphocytes that detect a large variety of bacteria and yeasts. This recognition depends on the detection of microbial compounds presented by the evolutionarily conserved major-histocompatibility-complex (MHC) class I molecule, MR1. Here we show that MAIT cells display cytotoxic activity towards MR1 overexpressing non-hematopoietic cells cocultured with bacteria. The NK receptor, CD161, highly expressed by MAIT cells, modulated the cytokine but not the cytotoxic response triggered by bacteria infected cells. MAIT cells are also activated by and kill epithelial cells expressing endogenous levels of MRI after infection with the invasive bacteria Shigella flexneri. In contrast, MAIT cells were not activated by epithelial cells infected by Salmonella enterica Typhimurium. Finally, MAIT cells are activated in human volunteers receiving an attenuated strain of Shigella dysenteriae-1 tested as a potential vaccine. Thus, in humans, MAIT cells are the most abundant T cell subset able to detect and kill bacteria infected cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dysentery, Bacillary / immunology*
  • Dysentery, Bacillary / pathology
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Female
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunity, Mucosal*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Male
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily B / immunology
  • Salmonella Infections / immunology*
  • Salmonella Infections / pathology
  • Salmonella typhimurium / immunology*
  • Shigella dysenteriae / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Histocompatibility Antigens Class I
  • KLRB1 protein, human
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily B

Grant support

This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM) and the Curie Institute, as well as grants obtained from Agence Nationale de la Recherche (ANR), Association François Aupetit (AFA) for Crohn's and colitis research. OL's group is “Equipe labellisée de la Ligue Contre le Cancer”. LLB received a long-term fellowship from the European molecular biology organization (EMBO). MD and AB received a PhD fellowship from La Ligue Contre le Cancer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.