Chlamydia trachomatis is a sexually transmitted pathogen that is a principal cause of pelvic inflammatory disease and female reproductive failure (infertility and miscarriage). The immunopathology of C. trachomatis-associated reproductive failure is not completely known. Whereas active C. trachomatis infections of the lower genital tract are routinely diagnosed and treated, occult disease as evidenced by C. trachomatis DNA in the upper genital tract has only recently been described. We hypothesize that chronic subclinical disease as evidenced by persistent C. trachomatis in the endometrium of women causes reproductive failure by stimulating a local T Helper 1-cytokine mediated immune response. Cytokines associated with T Helper 1-immunity can disrupt reproductive function at several levels both before and after implantation. The overall objectives of this project are: 1) to determine the prevalence of occult C. trachomatis (chlamydial DNA) in the endometrium of women undergoing in vitro fertilization for tubal factor infertility and in women with a history of unexplained recurrent spontaneous abortion compared to women with successful reproductive histories; 2) to characterize local cellular immunity in the endometrium of these women; and 3) to correlate the presence of C. trachomatis DNA and parameters of T Helper 1-immunity with subsequent reproductive success and failure.

Project Start
1998-07-01
Project End
1999-06-30
Budget Start
Budget End
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Ketterer, Margaret R; Rice, Peter A; Gulati, Sunita et al. (2016) Desialylation of Neisseria gonorrhoeae Lipooligosaccharide by Cervicovaginal Microbiome Sialidases: The Potential for Enhancing Infectivity in Men. J Infect Dis 214:1621-1628
Agarwal, Sarika; Sebastian, Shite; Szmigielski, Borys et al. (2008) Expression of the gonococcal global regulatory protein Fur and genes encompassing the Fur and iron regulon during in vitro and in vivo infection in women. J Bacteriol 190:3129-39
Sagar, Manish; Wu, Xueling; Lee, Sandra et al. (2006) Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J Virol 80:9586-98
Shen, Li; Feng, Xiaogeng; Yuan, Yuan et al. (2006) Selective promoter recognition by chlamydial sigma28 holoenzyme. J Bacteriol 188:7364-77
Sagar, Manish; Kirkegaard, Erin; Lavreys, Ludo et al. (2006) Diversity in HIV-1 envelope V1-V3 sequences early in infection reflects sequence diversity throughout the HIV-1 genome but does not predict the extent of sequence diversity during chronic infection. AIDS Res Hum Retroviruses 22:430-7
Wu, Hsing-Ju; Seib, Kate L; Srikhanta, Yogitha N et al. (2006) PerR controls Mn-dependent resistance to oxidative stress in Neisseria gonorrhoeae. Mol Microbiol 60:401-16
Seib, Kate L; Wu, Hsing-Ju; Kidd, Stephen P et al. (2006) Defenses against oxidative stress in Neisseria gonorrhoeae: a system tailored for a challenging environment. Microbiol Mol Biol Rev 70:344-61
Porter, Edith; Yang, Huixia; Yavagal, Sujata et al. (2005) Distinct defensin profiles in Neisseria gonorrhoeae and Chlamydia trachomatis urethritis reveal novel epithelial cell-neutrophil interactions. Infect Immun 73:4823-33
Wu, Hsing-Ju; Seib, Kate L; Edwards, Jennifer L et al. (2005) Azurin of pathogenic Neisseria spp. is involved in defense against hydrogen peroxide and survival within cervical epithelial cells. Infect Immun 73:8444-8
Seib, Kate L; Simons, Mark P; Wu, Hsing-Ju et al. (2005) Investigation of oxidative stress defenses of Neisseria gonorrhoeae by using a human polymorphonuclear leukocyte survival assay. Infect Immun 73:5269-72

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