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

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 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.Mucosal Immunology _#####################_ ; https://doi.

MAIT cell activation and dynamics associated with COVID-19 disease severity

“…A notable pattern in the airway scRNAseq data was that the MAIT cell cluster displayed an IL-17A-biased profile and was the main T cell cluster expressing IL17A transcript. Previous studies have shown that mucosal tissue MAIT cells have an IL-17-biased proinflammatory profile with less IFN- expression (23,46) and can contribute to IL-17-mediated inflammation during bacterial pneumonia (47). The setting of COVID-19 is, however, quite distinct in that SARS-CoV-2 infection of the lung is unlikely to give rise to MR1-presented antigens.…”

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

“…In humans, MAIT cell responses during infection have been suggested by studies of MAIT cells in patient cohorts, including in the blood and an increasing selection of tissues, paired with subsequent in vitro analysis. These studies included patients with tuberculosis, Helicobacter infection, cholera , and undefined infections such as sepsis and community-acquired pneumonia ( 77 – 80 ). MAIT cells were also activated in human volunteers infected with live Salmonella enterica Paratyphi A vaccine ( 66 ).…”

“…Different cytokine signals synergize to control MAIT responses ( 104 ), and thus, the MAIT cell functional capacity may differ in tissue settings compared to blood MAIT cells ( 105 ). In humans, most peripheral blood MAIT cells display type-1 responses upon stimulation, whereas in tissues a IL-17-secreting population is more readily detected ( 80 , 105 ), suggesting there may be functional differences. Following infection with S .…”

Mucosal-Associated Invariant T Cells as a Possible Target to Suppress Secondary Infections at COVID-19

“…No information regarding the increased values of IL-18, IL-12, or IL-15 in patients with COVID-19 was found and, therefore, this possible activation pathway requires further study. On the other hand, the role of MAIT cells resident in lung tissue in children with community-acquired pneumonia was demonstrated (10). Immunity profiling showed that MAIT cells from the bronchoalveolar lavages, but not from the blood, actively produced IL-17.…”

“…It is important that most patients were diagnosed with adenovirus and Mycoplasma pneumoniae while neither adenovirus nor mycoplasma synthesize riboflavin. The authors suggested that MAIT cells were probably activated through commensal microorganisms or co-infecting bacteria in combination with inflammatory cytokines (10). Since only MAIT cells resident in lung tissue but not derived from the blood produced IL-17, the contribution of co-infecting bacteria appears to be more important.…”