IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia
- Author(s)
- Lu, B; Liu, M; Wang, J; FAN, H; Yang, D; Zhang, L; Gu, X; Nie, J; Chen, Z; Corbett, AJ; Zhan, MJ; Zhang, S; Bryant, VL; Lew, AM; McCluskey, J; Luo, HB; Cui, J; Zhang, Y; Zhan, Y; Lu, G;
- 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
- Research Division(s)
- Immunology
- PubMed ID
- 32112047
- Publisher's Version
- https://doi.org/10.1038/s41385-020-0273-y
- Open Access at Publisher's Site
https://doi.org/10.1038/s41385-020-0273-y- NHMRC Grants
- NHMRC/1105209, NHMRC/1143976, NHMRC/1037321, NHMRC/1080321,
- Terms of Use/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