Identification of antimicrobial molecules released by Th17 targeting both Gram positive and Gram negative bacteria

Abstract

Abstract TH17 cell subpopulations have been defined that contribute to inflammation and homeostasis, yet the characteristics of TH17 cells that contribute to host defense against infection are not clear. To elucidate the antimicrobial machinery of the TH17 subset, we studied the response to Cutibacterium acnes, a skin commensal that is resistant to IL-26, the only known TH17 secreted protein with direct antimicrobial activity. We generated C. acnes-specific antimicrobial TH17 clones (AMTH17) with varying antimicrobial activity against C. acnes. A combination of RNA-seq and informatics analysis unraveled the transcriptional and antimicrobial gene profiles present in modules associated with the AMTH17 vs. non-antimicrobial TH17 cells. The expression of antimicrobial genes such as GNLY, GZMB, HIST2H2B also correlated with secreted antimicrobial proteins as measured by ELISA, and antimicrobial activity as determined in CFU assays. Scanning electron microscopy reveal that AMTH17s can release antimicrobial molecules that kill C. acnes and other Gram-positive and Gram-negative bacteria. Our study identifies a functionally distinct subpopulation of TH17 cells with an ability to secrete antimicrobial proteins in order to capture and kill bacteria.