Neutrophils suppress mucosal-associated invariant T cells in humans

Eur J Immunol. 2020 May;50(5):643-655. doi: 10.1002/eji.201948394. Epub 2020 Feb 3.

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that are abundant in mucosal tissues and the liver where they can respond rapidly to a broad range of riboflavin producing bacterial and fungal pathogens. Neutrophils, which are recruited early to sites of infection, play a nonredundant role in pathogen clearance and are crucial for controlling infection. The interaction of these two cell types is poorly studied. Here, we investigated both the effect of neutrophils on MAIT cell activation and the effect of activated MAIT cells on neutrophils. We show that neutrophils suppress the activation of MAIT cells by a cell-contact and hydrogen peroxide dependent mechanism. Moreover, highly activated MAIT cells were able to produce high levels of TNF-α that induced neutrophil death. We therefore provide evidence for a negative regulatory feedback mechanism in which neutrophils prevent overactivation of MAIT cells and, in turn, MAIT cells limit neutrophil survival.

Keywords: MAIT cells; Mucosal immunity; Neutrophils; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication / immunology*
  • Cell Movement
  • Coculture Techniques
  • Escherichia coli / immunology
  • Feedback, Physiological*
  • Humans
  • Hydrogen Peroxide / immunology
  • Hydrogen Peroxide / metabolism
  • Immunity, Mucosal*
  • Leukocyte Count
  • Liver / cytology
  • Liver / immunology
  • Lymphocyte Activation
  • Mucosal-Associated Invariant T Cells / cytology
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Hydrogen Peroxide