Pathogenesis of Genital Tract Disease Due toChlamydia trachomatis

Abstract

Although the pathologic consequences of C. trachomatis genital infection are well-established, the mechanism(s) that result in chlamydia-induced tissue damage are not fully understood. We have reviewed in vitro, animal, and human data related to the pathogenesis of chlamydial disease in an effort to better understand how reproductive sequelae result from C. trachomatis infection. Abundant in vitro data suggest the inflammatory response to chlamydiae is initiated and sustained by actively infected non-immune host epithelial cells. The mouse model indicates a critical role for chlamydia-activation of the innate immune receptor, toll-like receptor 2 (TLR2), and subsequent inflammatory cell influx and activation which contributes to the development of chronic genital tract tissue damage. Data from recent vaccine studies in the murine model and from human immunoepidemiologic studies support a role for chlamydia-specific CD4 Th1-IFN-γ-producing cells in protection from infection and disease. However, limited evidence obtained using animal models of repeated infection indicates that while the adaptive T cell response is a key mechanism involved in controlling or eliminating infection, it may have a double-edged nature, and contribute to tissue damage. Important immunologic questions include whether anamnestic CD4 T cell responses drive disease rather than protect against disease, and the role of specific immune cells and inflammatory mediators in the induction of tissue damage with primary and repeated infections. Continued study of the complex molecular and cellular interactions between chlamydiae and their host, and large-scale prospective immunoepidemiologic and immunopathologic studies are needed to address gaps in our understanding of pathogenesis, which thwart development of optimally effective control programs including vaccine development.

Chlamydial Intracellular Survival Strategies

“…However, inflammatory responses resulting from recurring infections or when bacteria access sterile sites (i.e., the upper genital tract) contribute to the detrimental scarring and pathology observed in some infected individuals (Stephens 2003;Darville and Hiltke 2010).…”

The glycolipid exoantigen derived from Chlamydia muridarum activates invariant natural killer T cells

“…1 In addition, C. trachomatis can also act as a precipitating factor in pathogenesis of human immunodeficiency virus and human papilloma virus infections. 2,3 Further, C. pneumoniae causes respiratory diseases like bronchitis, sinusitis and pneumonia. Recently, C. pneumoniae has also been implicated in the pathogenesis of atherosclerosis, Alzheimer's disease and multiple sclerosis.…”

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

“…Although the pathological consequences of infection are well known, the mechanisms of how chlamydia overcomes these host immunities are not fully understood. Notably, many host factors were proposed and identified in vitro and in vivo to play crucial roles for controlling chlamydia infection in the genital tract environment [36,44,47,48], including antimicrobial peptides, complement, and cytokines and chemokines that are stimulated following chlamydia infection. Besides those factors, it is important to note that T cell accumulation at the site of chlamydial infection also demonstrates a critical step for restricting chlamydial infection, as reported previously [49][50][51].…”