Pelvic inflammatory disease (PID) is defined as an infection of the endometrium, fallopian tubes, and adjacent structures that is caused by the ascension of microorganisms from the lower to upper genital tract The microorganism most convincingly associated with PID is Chlamydia trachomatis, and our proposal would provide the exciting opportinity for a discovery of the antigen-specific cell mediated immune resposes that are most strongly associated with protection against C. trachomatis infection as well as the elucidation of the antigen specifc immune responses correlated with containment of C. trachomatis infection to the lower genital tract. The 200 women enrolled into this longitudinal investigation will be recruited from an acute PID cohort (Project 1) and from a cohort of women who are at high risk for endocervical infection with C. trachomatis (Project 4). Completion of our investigation will allow: 1. Better understanding of the CD4 T cell antigen-specific responses that are most strongly associated with protection from C. trachomatis infection at enrollment. 2. Better elucidation of the CD4 T cell antigen-specific responses that are most strongly correlated with protection from incident C. trachomatis infection. 3. Identification of novel chlamydia-specific T cell responses that are most strongly associated with the decreased likelihood of ascension of C. trachomatis from the lower to upper genital tract.

Public Health Relevance

Collection of this information will provide important new data regarding delineation of protective antigenspecific cell mediated immune responses and will provide critical input for C. trachomatis vaccine development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI084024-03
Application #
8314064
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$484,657
Indirect Cost
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Zheng, Xiaojing; O'Connell, Catherine M; Zhong, Wujuan et al. (2018) Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women. Front Cell Infect Microbiol 8:307
Zheng, Xiaojing; O'Connell, Catherine M; Zhong, Wujuan et al. (2018) Discovery of Blood Transcriptional Endotypes in Women with Pelvic Inflammatory Disease. J Immunol 200:2941-2956
Rahman, K Shamsur; Darville, Toni; Wiesenfeld, Harold C et al. (2018) Mixed Chlamydia trachomatis Peptide Antigens Provide a Specific and Sensitive Single-Well Colorimetric Enzyme-Linked Immunosorbent Assay for Detection of Human Anti-C. trachomatis Antibodies. mSphere 3:
Taylor, Brandie D; Zheng, Xiaojing; O'Connell, Catherine M et al. (2018) Risk factors for Mycoplasma genitalium endometritis and incident infection: a secondary data analysis of the T cell Response Against Chlamydia (TRAC) Study. Sex Transm Infect 94:414-420
Rahman, K Shamsur; Darville, Toni; Russell, Ali N et al. (2018) Comprehensive Molecular Serology of Human Chlamydia trachomatis Infections by Peptide Enzyme-Linked Immunosorbent Assays. mSphere 3:
Rahman, K Shamsur; Darville, Toni; Russell, Ali N et al. (2018) Discovery of Human-Specific Immunodominant Chlamydia trachomatis B Cell Epitopes. mSphere 3:
Taylor, Brandie D; Zheng, Xiaojing; Darville, Toni et al. (2017) Whole-Exome Sequencing to Identify Novel Biological Pathways Associated With Infertility After Pelvic Inflammatory Disease. Sex Transm Dis 44:35-41
Poston, Taylor B; Qu, Yanyan; Girardi, Jenna et al. (2017) A Chlamydia-Specific TCR-Transgenic Mouse Demonstrates Th1 Polyfunctionality with Enhanced Effector Function. J Immunol 199:2845-2854
Petrina, Melinda A B; Cosentino, Lisa A; Rabe, Lorna K et al. (2017) Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin. Anaerobe 47:115-119
Russell, Ali N; Zheng, Xiaojing; O'Connell, Catherine M et al. (2016) Identification of Chlamydia trachomatis Antigens Recognized by T Cells From Highly Exposed Women Who Limit or Resist Genital Tract Infection. J Infect Dis 214:1884-1892

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