Journal
MUCOSAL IMMUNOLOGY
Volume 13, Issue 5, Pages 824-835Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-020-0273-y
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Funding
- National Natural Science Foundation of China (NSFC) [31770978, 91742109]
- Science and Technology Program Project of Guangdong Province [2014A020212020]
- Guangzhou Women and Children's Medical Center [5001-3001032, 5001-3001060, 5001-3001061]
- Australian National Health & Medical Research Council [1105209, 1143976, 1037321, 1080321]
- Future Fellowship from the Australian Research Council [FT160100083]
- National Health and Medical Research Council of Australia [1080321, 1143976, 1105209] Funding Source: NHMRC
- Australian Research Council [FT160100083] Funding Source: Australian Research Council
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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 1 alpha (HIF-1 alpha), 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.
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