PDF(Pubmed)
Abstract：
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.
摘要：
逃避宿主先天免疫防御是沙眼衣原体感染的关键特征，沙眼衣原体颠覆这些途径的机制还不完全清楚。我们筛选了嵌合沙眼衣原体突变体文库，以寻找对干扰细胞自主免疫防御很重要的遗传因素。具有包涵膜蛋白CT135的预测截短的突变株对人细胞中的干扰素γ激活的免疫敏感。CT135的作用是防止宿主驱动的泛素和p62/SQSTM募集到包涵膜。在沙眼衣原体感染的非人灵长类动物模型中，一个缺乏CT135的菌株被迅速清除，强调这种毒力因子对沙眼衣原体发病机制的重要性。对原代猕猴细胞中CT135表型的分析显示，针对沙眼衣原体的细胞自主免疫防御在人类和非人灵长类动物之间是保守的，并且将机制发现与体内感染结果联系起来。
