Pseudomonas aeruginosa induces the generation of pathogenic IFNγ+Th17 cells that promote lung damage and chronic inflammation in cystic fibrosis
En palabras de los autores
Abstract Cystic fibrosis (CF) involves cycles of bacterial infection and sustained inflammation. IFNγ + Th17 cells are implicated in chronic inflammation, yet their role in CF remains undefined. Here we identify two pathogenic Th17 subsets, Th1/17 + and pro-inflammatory Th17 (pTh17) cells, selectively enriched in CF lungs colonized by Pseudomonas aeruginosa . These pathogenic subsets derive from protective conventional Th17 (cTh17) precursors and, following activation, directly disrupt pulmonary epithelial integrity and trigger exaggerated inflammatory responses. Transcriptomic and T cell receptor profiling reveal in situ reprogramming and clonal selection of Th1/17 + and pTh17 cells in CF lungs. Mechanistically, clinical P. aeruginosa strains persist within dendritic cells and induce a polarizing IL-1β/IL-23 cytokine axis that promotes IFNγ + Th17 differentiation over classical Th1 lineage commitment. P. aeruginosa early isolates, lacking chronic adaptation signatures, still potently reprogramme cTh17 cells, inducing a transcriptional programme that mirrors CF lung-resident Th1/17 + and pTh17 profiles. These findings show that P. aeruginosa subverts mucosal immunity and establishes a self-sustaining immunopathological loop, offering potential targets for CF precision therapies.
Apareció: sábado, 26 de septiembre. Nature Microbiology. Revista con revisión por pares.