Chu, Timothy H.Khairallah, CamilleShieh, JasonCho, RheaQiu, ZhijuanZhang, YueEskiocak, OnurThanassi, David G.Kaplan, Mark H.Beyaz, SemirYang, Vincent W.Bliska, James B.Sheridan, Brian S.2024-04-252024-04-252021-12-06Chu TH, Khairallah C, Shieh J, et al. γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans [published correction appears in PLoS Pathog. 2022 May 25;18(5):e1010586]. PLoS Pathog. 2021;17(12):e1010103. Published 2021 Dec 6. doi:10.1371/journal.ppat.1010103https://hdl.handle.net/1805/40215Yersinia pseudotuberculosis is a foodborne pathogen that subverts immune function by translocation of Yersinia outer protein (Yop) effectors into host cells. As adaptive γδ T cells protect the intestinal mucosa from pathogen invasion, we assessed whether Y. pseudotuberculosis subverts these cells in mice and humans. Tracking Yop translocation revealed that the preferential delivery of Yop effectors directly into murine Vγ4 and human Vδ2+ T cells inhibited anti-microbial IFNγ production. Subversion was mediated by the adhesin YadA, injectisome component YopB, and translocated YopJ effector. A broad anti-pathogen gene signature and STAT4 phosphorylation levels were inhibited by translocated YopJ. Thus, Y. pseudotuberculosis attachment and translocation of YopJ directly into adaptive γδ T cells is a major mechanism of immune subversion in mice and humans. This study uncovered a conserved Y. pseudotuberculosis pathway that subverts adaptive γδ T cell function to promote pathogenicity.en-USAttribution 4.0 InternationalYersinia pseudotuberculosisIntestinal mucosaImmune subversionArticle