title: Influence of the tryptophan-indole-IFNγ axis on human genital Chlamydia trachomatis infection: role of vaginal co-infections.
abstract: 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.
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center New Orleans, LA, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Aiyar
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center New Orleans, LA, USA.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Quayle
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center New Orleans, LA, USA.
authors.forename: Lyndsey R
authors.initials: LR
authors.lastname: Buckner
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center New Orleans, LA, USA.
authors.forename: Shardulendra P
authors.initials: SP
authors.lastname: Sherchand
authors.affiliation: Department of Microbiology and Molecular Genetics, Public Health Research Institute Center, New Jersey Medical School-Rutgers, The State University of New Jersey Newark, NJ, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chang
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center New Orleans, LA, USA.
authors.forename: Arnold H
authors.initials: AH
authors.lastname: Zea
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Louisiana State University Health Sciences Center New Orleans, LA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Martin
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center Memphis, TN, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belland
mesh_terms: D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D060737:Reproductive Tract Infections / Q000276:immunology*; D014364:Tryptophan / Q000378:metabolism*; D014621:Vagina / Q000382:microbiology*
chemical_list: D007211:Indoles; D007371:Interferon-gamma; C030374:indole; D014364:Tryptophan
keywords: Chlamydia trachomatis; IDO1; IFNγ; bacterial vaginosis; indole; persistence; tryptophan; vaginal microbiome