title: Plac8-dependent and inducible NO synthase-dependent mechanisms clear Chlamydia muridarum infections from the genital tract.
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).
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. raymjohn@iupui.edu
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Johnson
authors.forename: Micah S
authors.initials: MS
authors.lastname: Kerr
authors.forename: James E
authors.initials: JE
authors.lastname: Slaven
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology* / Q000472:pathogenicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D060737:Reproductive Tract Infections / Q000276:immunology* / Q000382:microbiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; C475342:Plac8 protein, mouse; D011506:Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II