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C hlamydia ‐infected cells shed Gp 96 to prevent chlamydial re‐infection
Author(s) -
Karunakaran Karthika,
Subbarayal Prema,
Vollmuth Nadine,
Rudel Thomas
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13151
Subject(s) - biology , chlamydia trachomatis , microbiology and biotechnology , intracellular parasite , chlamydia , cell , chlamydiales , chlamydiaceae , intracellular , obligate , chlamydiae , virology , immunology , biochemistry , ecology
Summary C hlamydia 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 ( Gp 96), a chaperone for cell surface receptors, binds to and facilitates adherence and entry of C . trachomatis . Gp 96 expression was increased early in infection in a MAP kinase‐dependent way, thereby increasing chlamydial adherence and invasion. Gp 96 co‐precipitated with Protein Disulphide Isomerase ( PDI ), known to be involved in chlamydial host cell entry. During the replicative phase, Gp 96 was depleted from infected cells and shed into the supernatant by activation of metalloproteinase TACE ( ADAM 17). Loss of Gp 96 also reduced the activity of PDI on the cell surface. Reduced surface display of Gp 96 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 Gp 96 shedding in the protection of the chlamydial replicative niche.