IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia

Mucosal Immunol. 2020 Sep;13(5):824-835. doi: 10.1038/s41385-020-0273-y. Epub 2020 Feb 28.


Community-acquired pneumonia (CAP) contributes substantially to morbidity and mortality in children under the age of 5 years. In examining bronchoalveolar lavages (BALs) of children with CAP, we found that interleukin-17 (IL-17) production was significantly increased in severe CAP. Immune profiling showed that mucosal-associated invariant T (MAIT) cells from the BALs, but not blood, of CAP patients actively produced IL-17 (MAIT17). Single-cell RNA-sequencing revealed that MAIT17 resided in a BAL-resident PLZFhiCD103+ MAIT subset with high expression of hypoxia-inducible factor 1α (HIF-1α), reflecting the hypoxic state of the inflamed tissue. CAP BALs also contained a T-bet+ MAIT1 subset and a novel DDIT3+ (DNA damage-inducible transcript 3-positive) MAIT subset with low expression of HIF1A. Furthermore, MAIT17 differed from T-helper type 17 (Th17) cells in the expression of genes related to tissue location, innateness, and cytotoxicity. Finally, we showed that BAL monocytes were hyper-inflammatory and elicited differentiation of MAIT17. Thus, tissue-resident MAIT17 cells are induced at the infected respiratory mucosa, likely influenced by inflammatory monocytes, and contribute to IL-17-mediated inflammation during CAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Child
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunophenotyping
  • Inflammation Mediators / metabolism
  • Interleukin-17 / biosynthesis*
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Monocytes / immunology
  • Monocytes / metabolism
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism*
  • Pneumonia / etiology
  • Pneumonia / immunology*
  • Pneumonia / metabolism*
  • Pneumonia / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Transcription Factors / metabolism
  • Transcriptome


  • Biomarkers
  • Cytokines
  • IL17A protein, human
  • Inflammation Mediators
  • Interleukin-17
  • Transcription Factors