Chlamydia trachomatis (Ct), is the leading cause of bacterial sexually transmitted infections in the U.S., with increasing incidence rates over the las 10-15 years. A bench-to-bedside solution for a preventative vaccine for Ct is not available. Knowledge of inherent host molecular mechanisms that may influence host immunity will be helpful in improving down-selection of putative anti-Ct vaccine candidate(s). To this end, there is growing consensus on the role of small non-coding species of regulatory RNA, i.e. microRNAs (miRs) in critical processes including immunity and reproductive biology. Additionally, vaccination strategies or immunotherapy using miRs have now been established. Our recent report on the role of miR modulating host immunity and association studies on Ct-miR(s) collectively highlight the importance of these immune modulators in Ct infections and underscores the need to define their contribution in anti-Ct immunity. In this proposal, we plan to investigate specifically, the role of miR-182 in colonization of Chlamydia muridarum (Cm) via regulation of host protein, Alpha-2HS-Glycoprotein (AHSG) in the murine genital tract. Additionally, we plan to investigate the regulation of miR-182-AHSG in vaccinated mice where antigen (Ag)-specific CD4+T cells and interferon-? (IFN- ?) in accelerate Cm clearance from the genital tract. Taken together, this application aims at providing novel information on the role of miR-182 in chlamydial infections and modulation of miR-182 and its host targets by anti-Ct immunity.

Public Health Relevance

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide. In this proposal, we plan to specifically investigate the role of microRNA-182 in genital chlamydial infections. This proposal will provide insight(s) into the specific role of host microRNAs in the colonization of C. trachomatis in genital tract and the role of vaccine mediated protection in regulating miR-182 following C. trachomatis infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI117714-01A1
Application #
9036191
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Hiltke, Thomas J
Project Start
2016-07-14
Project End
2018-06-30
Budget Start
2016-07-14
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$73,500
Indirect Cost
$23,500
Name
University of Texas Health Science Center San Antonio
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
800189185
City
San Antonio
State
TX
Country
United States
Zip Code
78249
Keck, Jonathon; Gupta, Rishein; Christenson, Lane K et al. (2017) MicroRNA mediated regulation of immunity against gram-negative bacteria. Int Rev Immunol 36:287-299