IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia
Bingtai Lu, Ming Liu, Jun Wang, Huifeng Fan, Diyuan Yang, Li Zhang, Xiaoqiong Gu, Junli Nie, Zhenjun Chen, Alexandra J. Corbett, Michael J. Zhan, Shengbo Zhang, Vanessa L. Bryant, Andrew M. Lew, James McCluskey, Hai‐Bin Luo, Jun Cui, Yuxia Zhang, Yifan Zhan, Gen Lu
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 1 (HIF-1), 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.