Plac8-dependent and iNOS-dependent mechanisms clear Chlamydia muridarum infections from the genital tract

dc.contributor.authorJohnson, Raymond M.
dc.contributor.authorKerr, Micah S.
dc.contributor.authorSlaven, James E.
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2025-07-21T08:13:20Z
dc.date.available2025-07-21T08:13:20Z
dc.date.issued2012
dc.description.abstractChlamydia trachomatis urogenital serovars replicate predominantly in genital tract epithelium. This tissue tropism poses a unique challenge for host defense and vaccine development. Studies utilizing the Chlamydia muridarum mouse model have shown that CD4 T cells are critical for clearing genital tract infections. In vitro studies have shown that CD4 T cells terminate infection by upregulating epithelial inducible NO synthase (iNOS) transcription and NO production. However, this mechanism is not critical, as iNOS-deficient mice clear infections normally. We recently showed that a subset of Chlamydia-specific CD4 T cell clones could terminate replication in epithelial cells using an iNOS-independent mechanism requiring T cell degranulation. We advance that work using microarrays to compare iNOS-dependent and iNOS-independent CD4 T cell clones. Plac8 was differentially expressed by clones having the iNOS-independent mechanism. Plac8-deficient mice had delayed clearance of infection, and Plac8-deficient mice treated with the iNOS inhibitor N-monomethyl-l-arginine were largely unable to resolve genital tract infections over 8 wk. These results demonstrate that there are two independent and redundant T cell mechanisms for clearing C. muridarum genital tract infections: one dependent on iNOS, and the other dependent on Plac8. Although T cell subsets are routinely defined by cytokine profiles, there may be important subdivisions by effector function, in this case CD4(Plac8).
dc.eprint.versionAuthor's manuscript
dc.identifier.citationJohnson RM, Kerr MS, Slaven JE. Plac8-dependent and inducible NO synthase-dependent mechanisms clear Chlamydia muridarum infections from the genital tract. J Immunol. 2012;188(4):1896-1904. doi:10.4049/jimmunol.1102764
dc.identifier.urihttps://hdl.handle.net/1805/49602
dc.language.isoen_US
dc.publisherOxford University Press
dc.relation.isversionof10.4049/jimmunol.1102764
dc.relation.journalJournal of Immunology
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectChlamydia muridarum
dc.subjectReproductive tract infections
dc.subjectFemale genitalia
dc.subjectEpithelial cells
dc.subjectNitric oxide
dc.titlePlac8-dependent and iNOS-dependent mechanisms clear Chlamydia muridarum infections from the genital tract
dc.typeArticle
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