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| Status |
Public on Mar 14, 2012 |
| Title |
Plac8-dependent and iNOS-dependent T cell-mediate mechanisms clear Chlamydia muridarum infections from the genital tract |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Comparison of two Chlamydia-specific CD4 T cells that are dependent on iNOS to terminate Chlamydia replication in epithelial cells to two Chlamydia-specific CD4 T cells that are iNOS-independent: Chlamydia trachomatis urogenital serovars replicate predominately in epithelial cells lining the reproductive tract. This tissue tropism poses a unique challenge for the host immune system and vaccine development. Studies utilizing the Chlamydia muridarum mouse model have shown that CD4 T cells are critical and sufficient to clear primary genital tract infections. In vitro studies have shown that CD4 T cells terminate the infection in epithelial cells by up regulating epithelial iNOS transcription and nitric oxide production via IFN-gamma and T cell-epithelial cell interactions mediated by LFA-1-ICAM-1. This mechanism however is not critical as iNOS-deficient mice clear infections normally, and IFN-gamma deficient mice clear 99.9% of the infection with near normal kinetics. We recently showed that a subset of Chlamydia-specific CD4 T cell clones were able to terminate replication in epithelial cells using a mechanism that was independent of iNOS and IFN-gamma. That mechanism did not require physical lysis of infected cells, but instead required T cell degranulation. In this study we advanced that work using gene expression microarrays to compare CD4 T cell clones that are able to terminate epithelial replication via an iNOS-independent mechanism to iNOS-dependent CD4 T cell clones. Micro array experiments showed that Plac8 was differentially expressed by the T cell clones having the iNOS-independent mechanism. Plac8-deficient mice had significantly delayed clearance of C. muridarum genital tract infections, and that the large majority of Plac8-deficient mice treated with the iNOS-inhibitor N-monomethyl-L-arginine (MLA) were unable to resolve a C. muridarum genital tract infection over 8 weeks. These results demonstrate that there are two independent and redundant T cell mechanisms for clearing C. muridarum genital tract infections; one mechanism dependent on iNOS, the other mechanism dependent on Plac8. While T cells subsets have been defined by cytokine profiles, there are important subdivisions by effector functions, in this case CD4Plac8.
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| Overall design |
Gene expression study using 4 experimental groups with 4 replicates each.
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| |
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| Contributor(s) |
Johnson RM, Kerr M, Slaven J |
| Citation(s) |
22238459, 28634196 |
| |
| Submission date |
Sep 14, 2011 |
| Last update date |
Jul 11, 2019 |
| Contact name |
Raymond Morris Johnson |
| E-mail(s) |
raymond.johnson@yale.edu
|
| Organization name |
Yale University
|
| Department |
Med/Infectious Diseases
|
| Street address |
PO Box 208022
|
| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06520-8022 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA147435 |
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