Plac8-dependent and iNOS-dependent mechanisms clear Chlamydia muridarum infections from the genital tract
dc.contributor.author | Johnson, Raymond M. | |
dc.contributor.author | Kerr, Micah S. | |
dc.contributor.author | Slaven, James E. | |
dc.contributor.department | Medicine, School of Medicine | |
dc.date.accessioned | 2025-07-21T08:13:20Z | |
dc.date.available | 2025-07-21T08:13:20Z | |
dc.date.issued | 2012 | |
dc.description.abstract | Chlamydia 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.version | Author's manuscript | |
dc.identifier.citation | Johnson 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.uri | https://hdl.handle.net/1805/49602 | |
dc.language.iso | en_US | |
dc.publisher | Oxford University Press | |
dc.relation.isversionof | 10.4049/jimmunol.1102764 | |
dc.relation.journal | Journal of Immunology | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Chlamydia muridarum | |
dc.subject | Reproductive tract infections | |
dc.subject | Female genitalia | |
dc.subject | Epithelial cells | |
dc.subject | Nitric oxide | |
dc.title | Plac8-dependent and iNOS-dependent mechanisms clear Chlamydia muridarum infections from the genital tract | |
dc.type | Article |