Abstract
Chlamydia trachomatis is a Gram-negative bacterial pathogen and a major cause of sexually transmitted disease and preventable blindness. In women, infections with C. trachomatis may lead to pelvic inflammatory disease (PID), ectopic pregnancy, chronic pelvic pain, and infertility. In addition to infecting the female reproductive tract (FRT), Chlamydia spp. are routinely found in the gastro-intestinal (GI) tract of animals and humans and can be a reservoir for reinfection of the FRT. Whether Chlamydia disseminates from the FRT to the GI tract via internal routes remains unknown. Using mouse-specific C. muridarum as a model pathogen we show that Chlamydia disseminates from the FRT to the GI tract in a stepwise manner, by first infecting the FRT-draining iliac lymph nodes (ILNs), then the spleen, then the GI tract. Tissue CD11c+ DCs mediate the first step: FRT to ILN Chlamydia transport, which relies on CCR7:CCL21/CCL19 signaling. The second step, Chlamydia transport from ILN to the spleen, also relies on cell transport. However, this step is dependent on cell migration mediated by sphingosine 1-phosphate (S1P) signaling. Finally, spleen to GI tract Chlamydia spread is the third critical step, and is significantly hindered in splenectomized mice. Inhibition of Chlamydia dissemination significantly reduces or precludes the induction of Chlamydia-specific serum IgG antibodies, presence of which is correlated with FRT pathology in women. This study reveals important insights in context of Chlamydia spp. pathogenesis and will inform the development of therapeutic targets and vaccines to combat this pathogen.
Highlights
Transmitted infections (STIs) remain a major health challenge worldwide
Using a mouse model of infection here we show that Chlamydia spreads to the GI tract in a stepwise manner, by first infecting the female reproductive tract (FRT)-draining iliac lymph nodes (ILNs), the spleen and the GI tract
Tissue DCs mediate the first step: FRT to ILN Chlamydia spread, which relies on CCR7:CCL21/CCL19 signaling
Summary
Transmitted infections (STIs) remain a major health challenge worldwide. Recently WHO estimated that about 1 million new STIs are acquired daily. In 2016, about 376 million new STIs were reported world-wide, of which 127 million were caused by Chlamydia [1]. C. muridarum has been widely used as a model to study both pathogenesis of and immunity to human-specific C. trachomatis. This is because intravaginal infections of mice with C. muridarum mimic C. trachomatis pathology in humans, which may result in hydrosalpinx and infertility [11,12,13,14]. Human specific chlamydial strains produce upper FRT pathologies in mice only when animals are inoculated with large doses of Chlamydia directly in the uterus or ovaries [16], which does not represent physiological conditions of human infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
