Chlamydia‐infected cells shed Gp96 to prevent chlamydial re‐infection
Chlamydia‐infected cells shed Gp96 to prevent chlamydial re‐infection
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衣原体感染的细胞脱落 Gp96 以防止衣原体再次感染
DOI：
10.1111/mmi.13151
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发表时间：
2015
影响因子：
3.6
通讯作者：
Rudel T
中科院分区：
文献类型：
--
作者：
Karunakaran K;Subbarayal P;Vollmuth N;Rudel T
沙眼衣原体是一种专性细胞内病原体，具有双相发育生命周期。感染性初级体（EB）进入宿主细胞，在那里它们转化为网状体（RB），利用细胞代谢物繁殖。在衣原体发育的复制阶段，受感染细胞的再感染可能会阻止感染性EB的形成，从而中断感染周期。在这里，我们报告了葡萄糖调节蛋白96（Gp96），细胞表面受体的伴侣，结合并促进沙眼衣原体的粘附和进入。Gp96表达在感染早期以MAP激酶依赖性方式增加，从而增加衣原体粘附和侵袭。Gp96与已知参与衣原体宿主细胞进入的蛋白质二硫化物异构酶（PDI）共沉淀。在复制期，Gp96从感染的细胞中耗尽，并通过金属蛋白酶TACE（ADAM 17）的活化而脱落到上清液中。Gp96的缺失也降低了细胞表面PDI的活性。Gp96的表面展示减少以TACE依赖性方式在细胞系中防止衣原体再感染，但也在来源于人菌毛的原代细胞中防止衣原体再感染，人菌毛是衣原体感染的天然部位。我们的数据表明感染诱导的Gp96脱落在保护衣原体复制生态位中的作用。
Chlamydia trachomatisis an obligate intracellular human pathogen with a biphasic developmental life cycle. The infectious elementary bodies (EBs) enter a host cell where they transform into reticulate bodies (RBs) that use cellular metabolites to multiply. Re‐infection of an infected cell during the replicative phase of chlamydial development may prevent formation of infectious EBs, interrupting the infectious cycle. Here, we report that Glucose Regulated Protein 96 (Gp96), a chaperone for cell surface receptors, binds to and facilitates adherence and entry ofC. trachomatis. Gp96 expression was increased early in infection in a MAP kinase‐dependent way, thereby increasing chlamydial adherence and invasion. Gp96 co‐precipitated with Protein Disulphide Isomerase (PDI), known to be involved in chlamydial host cell entry. During the replicative phase, Gp96 was depleted from infected cells and shed into the supernatant by activation of metalloproteinase TACE (ADAM17). Loss of Gp96 also reduced the activity of PDI on the cell surface. Reduced surface display of Gp96 prevented chlamydial re‐infection in a TACE‐dependent manner in cell lines but also in primary cells derived from human fimbriae, the natural site of chlamydial infection. Our data suggest a role of infection‐induced Gp96 shedding in the protection of the chlamydial replicative niche.
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