IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia
Journal Title
Mucosal Immunology
Publication Type
Journal epub ahead of print
Abstract
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 PLZF(hi)CD103(+) MAIT subset with high expression of hypoxia-inducible factor 1alpha (HIF-1alpha), 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.
Publisher
NPG
WEHI Research Division(s)
Immunology
PubMed ID
32112047
Open Access at Publisher's Site
https://doi.org/10.1038/s41385-020-0273-y
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-03-24 01:39:42
Last Modified: 2020-03-24 02:20:32
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