Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Chlamydia trachomatis Infection Control Programs: Lessons Learned and Implications for Vaccine Development

Chlamydia trachomatis control efforts that enhance detection and treatment of infected women may paradoxically increase susceptibility of the population to infection. Conversely, these surveillance programs lower incidences of adverse sequelae elicited by genital tract infection (e.g., pelvic inflammatory disease and ectopic pregnancy), suggesting enhanced identification and eradication of C. trachomatis simultaneously reduces pathogen-induced upper genital tract damage and abrogates formation of protective immune responses. In this paper, we detail findings from C. trachomatis infection control programs that increase our understanding of chlamydial immunoepidemiology and discuss their implications for prophylactic vaccine design

Endometrial leukocyte subpopulations associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis genital tract infection

OBJECTIVE: Characterize endometrial inflammation associated with common genital tract pathogens. STUDY DESIGN: Immunohistochemical characterization of endometrial leukocyte subpopulations from 37 controls and 45 women infected with Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis. RESULTS: Compared to uninfected women, endocervical infection with C. trachomatis, N. gonorrhoeae, or T. vaginalis was associated with significant increases in endometrial T cells, B cells, plasma cells, and polymorphonuclear leukocytes. Even more substantial increases in T cell, B cell, and plasma cell numbers were detected among women infected endocervically and endometrially with C. trachomatis. CONCLUSIONS: As lower genital tract C. trachomatis, N. gonorrhoeae, or T. vaginalis infections were associated with comparable increases in the same endometrial leukocyte subpopulations, our results suggest underappreciated involvement of T. vaginalis in upper genital tract inflammatory processes. The more robust inflammatory infiltrate associated with C. trachomatis endometrial ascension may offer insight into host inflammatory responses associated with pelvic inflammatory disease development

HIV, progestins, genital epithelial barrier function, and the burden of objectivity†

Abstract Contributions from a diverse set of scientific disciplines will be needed to help individuals make fully informed decisions regarding contraceptive choices least likely to promote HIV susceptibility. This commentary recaps contrasting interpretations of results from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial, a study that compared HIV risk in women using the progestin-only injectable contraceptive depot medroxyprogesterone acetate (DMPA) vs. two other contraceptive choices. It also summarizes results from basic and translational research that establish biological plausibility for earlier clinical studies that identified enhanced HIV susceptibility in women using DMPA.</jats:p

A caveat for T cell transfer studies: generation of cytotoxic anti-Thy1.2 antibodies in Thy1.1 congenic mice given Thy1.2+ tumors or T cells

Thy 1.1 congenic mice given Thy 1.2+ tumors or T cells generate cytotoxic anti-Thy 1.2 antibody responses that delete transferred Thy 1.2+ T-cells