Plac8-Dependent and Inducible NO Synthase-Dependent Mechanisms Clear Chlamydia muridarum Infections from the Genital Tract

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
The Journal of Immunology (Impact Factor: 4.92). 02/2012; 188(4):1896-904. DOI: 10.4049/jimmunol.1102764
Source: PubMed


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).

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Available from: James E Slaven, Jan 29, 2015
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    • "Had the Plac8-dependent mechanism been dependent on perforin, we would have expected MLA-treated perforin knockout mice to shed Chlamydia throughout the 8th week of the experiment; they did not. The delayed clearance in untreated or MLA-treated perforin knockout mice compared to wild type mice is unlikely to represent a compromised Plac8-dependent clearance mechanism that is strongly associated with the in vitro degranulation-dependent termination mechanism [13], [16]. Perforin’s contribution to bacterial clearance is not likely occurring through enhancing CD4 T cell termination of Chlamydia replication in epithelial cells as it does not appear to relevant to the Plac8-dependent mechanism and is detrimental to the iNOS-dependent mechanism. "
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