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

Author:

Picard Michele D.1,Bodmer Jean-Luc1,Gierahn Todd M.1,Lee Alexander1,Price Jessica1,Cohane Kenya1,Clemens Veronica1,DeVault Victoria L.1,Gurok Galina1,Kohberger Robert2,Higgins Darren E.3,Siber George R.1,Flechtner Jessica Baker1,Geisler William M.4

Affiliation:

1. Genocea Biosciences, Inc., Cambridge, Massachusetts, USA

2. Blair & Company, LLC, Greenwich, Connecticut, USA

3. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA

4. University of Alabama at Birmingham, Birmingham, Alabama, USA

Abstract

ABSTRACT Chlamydia 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 disease-specific 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-γ) 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.

Publisher

American Society for Microbiology

Subject

Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy

Reference57 articles.

1. WHO. 2012. Global incidence and prevalence of selected curable sexually transmitted infections—2008. World Health Organization Geneva Switzerland. http://apps.who.int/iris/bitstream/10665/75181/1/9789241503839_eng.pdf.

2. Centers for Disease Control and Prevention. 2014. Sexually transmitted disease surveillance 2013. Centers for Disease Control and Prevention, Atlanta, GA. http://www.cdc.gov/std/stats13/surv2013-print.pdf.

3. CDC Grand Rounds: Chlamydia prevention: challenges and strategies for reducing disease burden and sequelae;Centers for Disease Control and Prevention;MMWR Morb Mortal Wkly Rep,2011

4. Risk of Sequelae afterChlamydia trachomatisGenital Infection in Women

5. Trachoma vaccine field trials in The Gambia

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