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

• Published in: Mucosal immunology Vol. 13; no. 5; pp. 824 - 835
• Main Authors: Lu, Bingtai, Liu, Ming, Wang, Jun, Fan, Huifeng, Yang, Diyuan, Zhang, Li, Gu, Xiaoqiong, Nie, Junli, Chen, Zhenjun, Corbett, Alexandra J., Zhan, Michael J., Zhang, Shengbo, Bryant, Vanessa L., Lew, Andrew M., McCluskey, James, Luo, Hai-bin, Cui, Jun, Zhang, Yuxia, Zhan, Yifan, Lu, Gen
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2020; Elsevier Limited
• Subjects: Allergology; Alveoli; Animals; Antibodies; Biomarkers; Biomedical and Life Sciences; Biomedicine; Bronchus; Child; Children; Cytokines - metabolism; Cytotoxicity; Disease Models, Animal; Disease Susceptibility; DNA damage; Female; Gastroenterology; Gene Expression Profiling; Helper cells; Humans; Hypoxia; Hypoxia-inducible factor 1a; Immunology; Immunophenotyping; Inflammation; Inflammation Mediators - metabolism; Interleukin 17; Interleukin-17 - biosynthesis; Lymphocyte Activation - immunology; Lymphocytes T; Male; Mice; Monocytes; Monocytes - immunology; Monocytes - metabolism; Morbidity; Mucosal immunity; Mucosal-Associated Invariant T Cells - immunology; Mucosal-Associated Invariant T Cells - metabolism; Pneumonia; Pneumonia - etiology; Pneumonia - immunology; Pneumonia - metabolism; Pneumonia - pathology; Ribonucleic acid; RNA; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism; Transcription; Transcription Factors - metabolism; Transcriptome
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-020-0273-y

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 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.