Adaptive γδ T cell function is directly subverted by the Yersinia pseudotuberculosis outer protein YopJ
| Autor: | Timothy H Chu, Camille Khairallah, Jason Shieh, Rhea Cho, Zhijuan Qiu, Yue Zhang, Indralatha Jayatilaka, David Thanassi, Semir Beyaz, Vincent Yang, James Bliska, Brian S Sheridan |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 206:99.04-99.04 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.206.supp.99.04 |
| Popis: | Vγ4 T cells are an unconventional subset of T cells that protect the intestinal mucosa from pathogen invasion and capable of anamnestic responses. Yersinia pseudotuberculosis (Yptb) is a foodborne pathogen that invades through the intestinal mucosa and subverts immune function by translocation of Yersiniaouter protein (Yop) effectors into target cells. In this study, we evaluated the response of adaptive Vγ4 T cells to Yptb to determine if adaptive γδ T cells are a target of immune subversion. Tracking Yptb translocation of Yop effectors through a FRET-based reporter assay revealed targeted and preferential delivery of Yop effectors directly into adaptive γδ T cells inhibited anti-microbial IFNγ production. Using a series of recombinant Yptb deficient or defective in numerous pathogenicity genes revealed that direct subversion of the adaptive γδ T cell IFNγ response was mediated by the adhesion molecule YadA, the injectosome component YopB, and the YopJ effector. Thus, Yptb attachment and translocation of YopJ directly into adaptive γδ T cells is a major mechanism of γδ T cell subversion. RNA-Seq of adaptive γδ T cells revealed that a broad anti-pathogen gene signature was inhibited by translocation of YopJ and suggested a role of the STAT4 pathway in this process. Indeed, IL-12p40 promoted the adaptive γδ T cell IFNγ response and YopJ limited STAT4 phosphorylation levels. Importantly, circulating human Vδ2+T cells were similarly targeted and inhibited by the YopJ effector, highlighting a novel and conserved Yptb pathway that subverts adaptive γδ T cell function. |
| Databáze: | OpenAIRE |
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