Resolution of Chlamydia trachomatis Infection Is Associated with a Distinct T Cell Response Profile

Abstract

dChlamydia trachomatis is the causative agent of the most frequently reported bacterial sexually transmitted infection, the total burden of which is underestimated due to the asymptomatic nature of the infection. Untreated C. trachomatis infections can cause significant morbidities, including pelvic inflammatory disease and tubal factor infertility (TFI). The human immune response against C. trachomatis, an obligate intracellular bacterium, is poorly characterized but is thought to rely on cell-mediated immunity, with CD4؉ and CD8 ؉ T cells implicated in protection. In this report, we present immune profiling data of subjects enrolled in a multicenter study of C. trachomatis genital infection. CD4؉ and CD8 ؉ T cells from subjects grouped into diseasespecific cohorts were screened using a C. trachomatis proteomic library to identify the antigen specificities of recall T cell responses after natural exposure by measuring interferon gamma (IFN-␥) levels. We identified specific T cell responses associated with the resolution of infection, including unique antigens identified in subjects who spontaneously cleared infection and different antigens associated with C. trachomatis-related sequelae, such as TFI. These data suggest that novel and unique C. trachomatis T cell antigens identified in individuals with effective immune responses can be considered as targets for vaccine development, and by excluding antigens associated with deleterious sequelae, immune-mediated pathologies may be circumvented.

Risk of gastroschisis with maternal genitourinary infections: the US National birth defects prevention study 1997–2011

“…This difference in the genetically regulated response to an antigen may explain why not all STIs or UTIs during the critical time period of embryonic development result in the development of gastroschisis. For C. trachomatis , the immunogenetic response to the pathogen determines whether the infection will be cleared with or without a serious proinflammatory response 53–55…”

The relative contribution of causal factors in the transition from infection to clinical chlamydial disease

“…Finally, measuring the immune response directly will undoubtedly contribute to the modeling of disease progression. IFN-γ levels (often considered the primary driver of a protective chlamydial host response and optimal antibody-mediated immunity) 37 , 38 , T-cell responses 39 and B-cell responses 40 would all be valuable factors to investigate in future modeling. Despite the absence of these factors in the current analysis, an advantage of the approach taken in this study is that the models generated give an indication of the relative importance of both the factors considered and of the proportion of “missing” data yet to be investigated.…”

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

“…Both animal and human studies have established a vital role for T cell-mediated immunity, predominantly that of IFN- γ -producing CD4 + T cells, and the complementary role of humoral immunity in host resistance to chlamydial infection [4, 5]. CD8 + T cells have been shown to protect against infection when cultured ex vivo and transferred to naive animals, and immunization with recombinant vaccinia viruses expressing CD8 + T cell antigens from C. trachomatis conferred protection in mice [6]. Chlamydia vaccine research has led to the discovery of a large number of protective antigens [7–9].…”