IFN-gamma and IL-17 elicit synergistic anti-mycobacterial responses by inhibiting coronin-1A retention #MMPMID41353295
Park HS; Pham TA; Jiang Z; Choi S; Back YW; Jang IT; Shin KW; Son YJ; Choi HG; Kim HJ
Commun Biol 2025[Dec]; ? (?): ? PMID41353295show ga
CD4(+)IFN-gamma(+)IL-17(+) T cells and their secreted cytokines play a critical role in the anti-mycobacterial response. However, the underlying synergistic mechanism of IFN-gamma and IL-17 is little known. This study demonstrates that the downregulation of coronin-1A retention on the phagosome is a synergistic pathway for IFN-gamma and IL-17 that kills Mycobacterium tuberculosis (Mtb) in macrophages. IL-17 alone does not play a role in intracellular Mtb killing but potentiates the anti-mycobactericidal pathway of IFN-gamma. Co-treatment of IFN-gamma/IL-17 inhibited phosphorylation of STAT3, induced LRG47 expression, and reduced retention of coronin-1A on phagosome, thereby eliciting phagolysosomal fusion and bacterial killing, which was proved through response analysis of IFN-gamma/IL-17 in Mtb-infected macrophages transfected with small interfering RNA of coro1a, lrg47, or stat1. Determination of adjunctive therapeutic effect of IFN-gamma, IL-17, or both with anti-mycobacterial drugs showed that the bacterial load in the tissue of mice co-treated with IFN-gamma/IL-17, even at 1 ng/mL concentration each, was more rapidly reduced compared to those of IFN-gamma injection or chemotherapy alone. It inhibited the re-growth after treatment termination. Our results shed new light on the synergistic mechanisms of IFN-gamma/IL-17 for anti-mycobacterial responses, which might be targeted as an adjunctive chemotherapeutic method against tuberculosis.
Commun+Biol 2025 ; ? (?): ?
