Stimulation of a subset of natural killer T cells by CD103+ DC is required for GM-CSF and protection from pneumococcal infection

Cell Rep. 2022 Jan 11;38(2):110209. doi: 10.1016/j.celrep.2021.110209.

Abstract

Innate-like T cells, including invariant natural killer T cells, mucosal-associated invariant T cells, and γδ T cells, are present in various barrier tissues, including the lung, where they carry out protective responses during infections. Here, we investigate their roles during pulmonary pneumococcal infection. Following infection, innate-like T cells rapidly increase in lung tissue, in part through recruitment, but T cell antigen receptor activation and cytokine production occur mostly in interleukin-17-producing NKT17 and γδ T cells. NKT17 cells are preferentially located within lung tissue prior to infection, as are CD103+ dendritic cells, which are important both for antigen presentation to NKT17 cells and γδ T cell activation. Whereas interleukin-17-producing γδ T cells are numerous, granulocyte-macrophage colony-stimulating factor is exclusive to NKT17 cells and is required for optimal protection. These studies demonstrate how particular cellular interactions and responses of functional subsets of innate-like T cells contribute to protection from pathogenic lung infection.

Keywords: Streptococcus pneumoniae; T cell; cytokine; dendritic cell; innate; lung infection; natural killer T cell; γδ T cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dendritic Cells / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-17 / immunology
  • Intraepithelial Lymphocytes / immunology
  • Intraepithelial Lymphocytes / metabolism
  • Lung / immunology
  • Lung / microbiology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism*
  • Pneumococcal Infections / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Streptococcus pneumoniae / immunology

Substances

  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor