Discipline: Biological Sciences
Skyla A. Duncan - Alabama State University
Co-Author(s): Rajnish Sahu, Shree R. Singh and Vida A. Dennis
The major outer membrane protein (MOMP) of Chlamydia trachomatis (CT) is a very desirable vaccine candidate against CT because it stimulates robust T- and B-cell protective responses. Conversely, we showed that MOMP contributes to CT inflammation by stimulating macrophages to secrete pro-inflammatory cytokines that play pivotal roles in the pathogenesis of chlamydial diseases, and whose secretion levels are modulated by IL-10. We also showed that MOMP induced marked expression of the Socs3 gene in macrophages, correlating with its induction of pro-inflammatory cytokines, and its triggering of an M1 macrophage phenotype. Our goal in this study is to understand the inflammatory nature of MOMP by focusing on key chemokines (CCL5 and CXCL10), NO and Nod1/2 receptors, which are implicated in CT inflammation. We also evaluated their inhibition by IL-10 and its effect on M1 and M2 macrophage phenotypes. Mouse J774 macrophages were stimulated with recombinant MOMP (0.01-10 ug/mL) with/without exogenously added IL-10 (10 ng/mL); supernatants and RNA were collected for cytokine ELISAs, NO production and TaqMan gene expression analyses. Our results showed that rMOMP induced expression of CCL5, CXCL10, NO and Nod1/2 receptors that recognize and activate key inflammatory pathways, which were all modulated by IL-10. Characterization of macrophages revealed that rMOMP increased Nos2 expression, an M1 phenotypic marker, which was modulated by IL-10, suggesting skewing of the M1 phenotype whereas IL-10 upregulated M2 markers including, Arg 1 (and its isoform Arg 2) and Mrc1. Overall, our data helps in understanding the inflammatory nature of MOMP and the potential role played by M1 and M2 phenotypes in mediating IL-10 regulation of CT inflammation.Not Submitted
Funder Acknowledgement(s): This research was supported by funding from NSF-CREST grant (HRD-1241701). *Corresponding author: Vida A. Dennis, PhD, Center for NanoBiotechnology Research, Alabama State University, 1627 Harris Way, Montgomery, AL, 36104; Phone: (334)-229-8447: Email: firstname.lastname@example.org
Faculty Advisor: Dr. Vida A. Dennis, email@example.com
Role: All of it.