Protective Immunity toChlamydia trachomatisGenital Infection: Evidence from Human Studies

Abstract

Background Some screening and treatment programs implemented to control genital Chlamydia trachomatis infections and their complications have shown initial reductions in infection prevalence followed by rises to pre-program levels or higher. One hypothesis is that treatment shortens duration of infection, attenuates development of protective immunity and thereby increases risk of re-infection. Methods A literature review was undertaken to assess evidence supporting the concept of protective immunity, its characteristics and its laboratory correlates in human chlamydial infection. The discussion is organized around key questions formulated in preparation for the Chlamydia Immunology and Control Expert Advisory Meeting held by the Centers for Disease Control and Prevention in April, 2008. Results Definitive human studies are not available, but cross-sectional studies show chlamydia prevalence, organism load and concordance rates in couples decrease with age, and organism load is lower in those with repeat infections, supporting the concept of protective immunity. The protection appears partial and can be overcome upon re-exposure, similar to what is found in rodent models of genital infection. No data are available to define the duration of infection required to confer a degree of immunity or the time course of immunity following resolution of untreated infection. In longitudinal studies of African sex workers, a group presumed to have frequent and ongoing exposure to chlamydial infection, interferon gamma production by peripheral blood mononuclear cells in response to chlamydial heat shock protein 60 was associated with low risk of incident infection. In cross-sectional studies, relevant Th1 type responses are found in infected persons, paralleling the studies in animal models. Conclusions The data support the concept that some degree of protective immunity against re-infection develops following human genital infection, although it appears at best partial. It is likely that factors besides population levels of immunity contribute to trends in prevalence observed in screening and treatment programs. Future studies of protective immunity in humans will require longitudinal follow-up of individuals and populations, frequent biological and behavioral sampling and special cohorts to help control for exposure.

Microbiological Characteristics of Chlamydia trachomatis and Neisseria gonorrhoeae Infections in South African Women

“…Younger age and pregnancy were independently associated with a higher bacterial load of C. trachomatis and younger age and having had more than one sexual partner in the last 6 months with a higher load of N. gonorrhoeae. The same relation with age (for C. trachomatis) in several NAAT studies has been described before and might be due to changes in the cervical epithelium or to younger women being more sexually active and exhibiting riskier behavior or might reflect acquired immunity in adults (28)(29)(30). There were several limitations to our study.…”

Profile of Anti-Chlamydia Immune Responses in Complicated (Infertile) and Non-complicated (Fertile) Genital Infections

“…We tested the hypothesis that the anti-chlamydial immune effectors induced during infections that produce complications are qualitatively or quantitatively different from non-complicated infections. Our results are corroborated by previous reports on the analysis of anti-chlamydial cytokine response by Peripheral Blood Leukocytes (PBL) from infected women with and without tubal symptoms that indicated that chlamydial control in humans is Th1-mediated, involving IFN-γ; and that infections with complications are characterized by Th2 response marked with secretion of IL-4, IL-5 and IL-10 [28][29][30][31]. Accordingly, we found significantly greater levels of the Th1-type cytokines, TNF-α, IFN-γ and IL-17 in sera from infected mice that were protected from infertility than infected animals that developed infertility; and there were significantly greater levels of the Th2-type cytokines, IL-5 and IL-10, in the serum of infected mice that developed infertility than mice protected from infertility.…”

“…However, the results are similar to the cytokine measurements following antigen stimulation of PBL previously reported [21,30]. The key finding from this study therefore is that the results from analysis of immune profiles after genital chlamydial infection revealed that in experimental animals protection from tubal pathologies and infertility is associated with a predominantly Th1 response, which is corroborated by previous human studies using antigen-specific cytokine response by PB to chlamydial antigens [21,30].…”

“…The caspase inhibitors did not alter the cytokine levels in non-infected (naïve) animals. These results from experimental animal studies indicating that the development of complications such as infertility may affect the levels of Th1 and Th2 cytokines were corroborated by previous reports that chlamydial immunity in humans and mice is Th1 mediated [28][29][30][31].…”

“…The analysis of anti-chlamydial cytokine response by Peripheral Blood Leukocytes (PBL) from infected women with and without symptoms or tubal symptoms had indicated that chlamydial control in humans is Th1-mediated, involving IFN-γ; and infections with complications are characterized by Th2 response marked with secretion of IL-4, IL-5 and IL-10 [28][29][30][31]. In the mouse genital infection model system, the inbred animals are confined in relatively hygienic conditions, compared to outbred animals or humans.…”