The natural history of genital Chlamydia trachomatis
infections can vary widely;
infections can spontaneously resolve but can also last from months to years, potentially progressing to cause significant pathology. The host and bacterial factors underlying this wide variation are not completely understood, but emphasize the bacterium's capacity to evade/adapt to the genital immune response, and/or exploit local environmental conditions to survive this immune response. IFNγ is considered to be a primary host protective
cytokine against endocervical C. trachomatis
infections. IFNγ acts by inducing the host
enzyme indoleamine 2,3-dioxgenase, which catabolizes
tryptophan, thereby depriving the bacterium of this
essential amino acid. In vitro studies have revealed that
tryptophan deprivation causes Chlamydia to enter a viable but non-infectious growth pattern that is termed a persistent growth form, characterized by a unique morphology and gene expression pattern. Provision of
tryptophan can reactivate the bacterium to the normal developmental cycle. There is a significant difference in the capacity of ocular and genital C. trachomatis serovars to counter
tryptophan deprivation. The latter uniquely encode a functional
tryptophan synthase to synthesize
tryptophan via
indole salvage, should
indole be available in the
infection microenvironment. In vitro studies have confirmed the capacity of
indole to mitigate the effects of IFNγ; it has been suggested that a perturbed vaginal microbiome may provide a source of
indole in vivo. Consistent with this hypothesis, the microbiome associated with
bacterial vaginosis includes species that encode a
tryptophanase to produce
indole. In this review, we discuss the natural history of genital chlamydial
infections, morphological and molecular changes imposed by IFNγ on Chlamydia, and finally, the microenvironmental conditions associated with vaginal
co-infections that can ameliorate the effects of IFNγ on C. trachomatis.