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

Abstract

The simultaneous induction of protective and immunopathogenic responses during genital C. trachomatis infection is proposed to respectively confer partial immunity and at least partly drive the complications such as pelvic inflammatory disease and tubal factor infertility. T cell-mediated immune response is crucial for chlamydial immunity in experimental animal models and in humans. However, the levels of T cell-derived cytokines in human specimens such as serum or mucosal tissue fluids can be influenced by several factors in addition to the incident infection. Therefore, it is uncertain whether T cell cytokine levels in biological fluids can predict infections that lead to complications, and can be used as reliable biomarkers of chlamydial disease complications, such as tubal factor infertility. Using a reliable murine model of chlamydiainduced infertility, we tested the hypothesis that the anti-chlamydial T cell immune effectors induced during infections that produce complications are qualitatively or quantitatively distinct from non-complicated infections. The results revealed that infected infertile mice exhibited lower systemic anti-chlamydial total IgG levels than animals with comparable microbiological shedding of chlamydiae but protected from infertility by treatment with the pan-caspase inhibitor Z-VAD-FMK. Interestingly, infected fertile mice showed greater Th1-type cytokines, mostly TNF-α, IFN-γ and IL-17 than infertile animals, while levels of the Th2-type cytokines, IL-5 and IL-10 were higher in infected infertile mice than fertile mice. These profiles of systemic cytokine levels in mice are corroborated by clinical findings demonstrating that chlamydial infection with tubal pathologies elicited a predominantly Th2 immune response. Thus, antigen-specific T cell cytokine response may distinguish infections leading to immunity versus sequelae, providing a useful prognostic biomarker and as a guide for vaccine design and evaluation.

Capturing Complex Vaccine-Immune-Disease Relationships for Free-Ranging Koalas: Higher Chlamydial Loads Are Associated With Less IL17 Expression and More Chlamydial Disease

“…As multiple aspects of the koala immune response are poorly understood, researchers often refer to vaccine trials against two other chlamydial species, C. trachomatis or C. muridarum, where mice are most often used as host models of infection (22,23). Of these murine trials, the most commonly measured host cytokine in response to chlamydial infection is IFNγ (22), where the expression of IFNγ has been associated with protection against chlamydial disease (24). Increases in IFNγ concentration in vitro can lead to the degradation of tryptophan, leading to the starvation of C. trachomatis of this essential amino acid and inducing chlamydial persistence [an inactive, intracellular pathogen response to external stressors; (25)].…”

Capturing complex vaccine-immune-disease relationships for free-ranging koalas: IL17 production is an important intermediate factor against chlamydial disease

“…As multiple aspects of the koala immune response are poorly understood, researchers often refer to vaccine trials against two other chlamydial species, C. trachomatis or C. muridarum, where mice are most often used as host models of infection [18,19]. Of these murine trials, the most commonly measured host cytokine in response to chlamydial infection is IFNγ [18], where the production of IFNγ has been associated with protection against chlamydial disease [20].…”