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Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection (STI) in the USA. As an STI, C. trachomatis infections can cause inflammatory damage to the female reproductive tract and downstream sequelae including infertility. No vaccine currently exists to C. trachomatis, which evades sterilizing immune responses in its human host. A better understanding of this evasion will greatly benefit the production of anti-Chlamydia therapeutics and vaccination strategies. This minireview will discuss a single branch of the immune system, which activates in response to genital Chlamydia infection: so-called "cell-autonomous immunity" activated by the cytokine interferon-gamma. We will also discuss the mechanisms by which human and mouse-adapted Chlamydia species evade cell-autonomous immune responses in their native hosts. This minireview will examine five pathways of host defense and their evasion: (i) depletion of tryptophan and other nutrients, (ii) immunity-related GTPase-mediated defense, (iii) production of nitric oxide, (iv) IFNγ-induced cell death, and (v) RNF213-mediated destruction of inclusions., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Chlamydia trachomatis urogenital serovars are intracellular bacteria that parasitize human reproductive tract epithelium. As the principal cell type supporting bacterial replication, epithelial cells are central to Chlamydia immunobiology initially as sentries and innate defenders, and subsequently as collaborators in adaptive immunity-mediated bacterial clearance. In asymptomatic individuals who do not seek medical care a decisive struggle between C. trachomatis and host defenses occurs at the epithelial interface. For this study, we modeled the immunobiology of epithelial cells and macrophages lining healthy genital mucosa and inflamed/infected mucosa during the transition from innate to adaptive immunity. Upper reproductive tract epithelial cell line responses were compared to bone marrow-derived macrophages utilizing gene expression microarray technology. Those comparisons showed minor differences in the intrinsic innate defenses of macrophages and epithelial cells. Major lineage-specific differences in immunobiology relate to epithelial collaboration with adaptive immunity including an epithelial requirement for inflammatory cytokines to express MHC class II molecules, and a paucity and imbalance between costimulatory and coinhibitory ligands on epithelial cells that potentially limits sterilizing immunity (replication termination) to Chlamydia-specific T cells activated with limited or unconventional second signals., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chlamydia muridarum and Chlamydia trachomatis, mouse and human strains, respectively, have been used to study immunity in a murine model of female genital tract infection. Despite evidence that unique genes of these otherwise genomically similar strains could play a role in innate immune evasion in their respective mouse and human hosts, there have been no animal model findings to directly support this conclusion. Here, we infected C57BL/6 and adaptive immune-deficient Rag1(-/-) female mice with these strains and evaluated their ability to spontaneously resolve genital infection. Predictably, C57BL/6 mice spontaneously cleared infection caused by both chlamydial strains. In contrast, Rag1(-/-) mice which lack mature T and B cell immunity but maintain functional innate immune effectors were incapable of resolving C. muridarum infection but spontaneously cleared C. trachomatis infection. This distinct dichotomy in adaptive and innate immune-mediated clearance between mouse and human strains has important cautionary implications for the study of natural immunity and vaccine development in the mouse model., (© 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.)

Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide and leads to serious pathological sequelae in the upper genital tract (UGT) including pelvic inflammatory disease, ectopic pregnancy, and infertility. Several components of the host immune responses have been shown to contribute to the UGT pathology following genital chlamydial infection. We have shown recently that CD8(+) T cells induce the chlamydial UGT pathology via the production of TNF-α. However, those studies did not determine whether the pathology is mediated by bystander or antigen-specific CD8(+) T cells. In this study, we compared chlamydial clearance and UGT pathology in OT-1 transgenic mice and the corresponding C57BL/6J wild-type mice following primary intravaginal Chlamydia muridarum infection. All CD8(+) T cells in the OT-1 mice respond only to the Ova 257-264 peptide and are incapable of responding to other antigenic epitopes including those of Chlamydia. OT-1 mice displayed vaginal chlamydial clearance comparable to the wild-type animals. However, both oviduct and uterine horn pathology were minimal in the OT-1 mice compared with the high degree of pathology observed in the wild-type animals. These results strongly suggest that Chlamydia-specific, not bystander, CD8(+) T cells mediate the UGT pathological sequelae following genital chlamydial infection., (© 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)