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CT135 mediates the resistance of Chlamydia trachomatis to primate interferon gamma stimulated immune defenses.

Mark C Fernandez | Yvonne Cosgrove Sweeney | Robert J Suchland | Steven J Carrell | Olusegun O Soge | Isabelle Q Phan | Daniel D Rockey | Dorothy L Patton | Kevin Hybiske
iScience | 2024

Evading host innate immune defenses is a critical feature of Chlamydia trachomatis infections, and the mechanisms used by C. trachomatis to subvert these pathways are incompletely understood. We screened a library of chimeric C. trachomatis mutants for genetic factors important for interference with cell-autonomous immune defenses. Mutant strains with predicted truncations of the inclusion membrane protein CT135 were susceptible to interferon gamma-activated immunity in human cells. CT135 functions to prevent host-driven recruitment of ubiquitin and p62/SQSTM to the inclusion membrane. In a nonhuman primate model of C. trachomatis infection, a CT135-deficient strain was rapidly cleared, highlighting the importance of this virulence factor for C. trachomatis pathogenesis. Analysis of CT135 phenotypes in primary macaque cells revealed that cell-autonomous immune defenses against C. trachomatis are conserved between humans and nonhuman primates and connects mechanistic findings with in vivo infection outcomes.

Pubmed ID: 38947519 RIS Download

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