title: Chlamydia-infected cells shed Gp96 to prevent chlamydial re-infection.
abstract: Chlamydia trachomatis is 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 of C. 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.
authors.affiliation: Department of Microbiology, Biocenter, University of Wuerzburg, Am Hubland, Wuerzburg, D-97074, Germany.
authors.forename: Karthika
authors.initials: K
authors.lastname: Karunakaran
authors.affiliation: Department of Microbiology, Biocenter, University of Wuerzburg, Am Hubland, Wuerzburg, D-97074, Germany.
authors.forename: Prema
authors.initials: P
authors.lastname: Subbarayal
authors.affiliation: Department of Microbiology, Biocenter, University of Wuerzburg, Am Hubland, Wuerzburg, D-97074, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Vollmuth
authors.affiliation: Department of Microbiology, Biocenter, University of Wuerzburg, Am Hubland, Wuerzburg, D-97074, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D001422:Bacterial Adhesion; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; C053387:endoplasmin; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human