Type-I Interferon Signaling Protects against Chlamydia trachomatis Infection in the Female Lower Genital Tract

We have previously shown that Chlamydia trachomatis is significantly inhibited during the early stage of infection in the female mouse lower genital tract and the anti-C. trachomatis innate immunity is compromised in the absence of cGAS-STING signaling. Since type-I interferon is a major downstream response of the cGAS-STING signaling, we evaluated the effect of type-I interferon signaling on C. trachomatis infection in the female genital tract in the current study. The infectious yields of chlamydial organisms recovered from vaginal swabs along the infection course were carefully compared between mice with or without deficiency in type-I interferon receptor (IFN alpha R1) following intravaginal inoculation with 3 different doses of C. trachomatis. It was found that IFN alpha R1-deficient mice significantly increased the yields of live chlamydial organisms on days 3 and 5, providing the 1st experimental evidence for a protective role of type-I interferon signaling in preventing C. trachomatis infection in mouse female genital tract. Further comparison of live C. trachomatis recovered from different genital tract tissues between wild type and IFN alpha R1-deficient mice revealed that the type-I interferon-dependent anti-C. trachomatis immunity was restricted to mouse lower genital tract. This conclusion was validated when C. trachomatis was inoculated transcervically. Thus, we have demonstrated an essential role of type-I interferon signaling in innate immunity against C. trachomatis infection in the mouse lower genital tract, providing a platform for further revealing the molecular and cellular basis of type-I interferon-mediated immunity against sexually transmitted infection with C. trachomatis. We have previously shown that Chlamydia trachomatis is significantly inhibited during the early stage of infection in the female mouse lower genital tract and the anti-C. trachomatis innate immunity is compromised in the absence of cGAS-STING signaling. Since type-I interferon is a major downstream response of the cGAS-STING signaling, we evaluated the effect of type-I interferon signaling on C. trachomatis infection in the female genital tract in the current study.

Automated summary

We found that Chlamydia trachomatis is inhibited during early infection in the female mouse genital tract and that the innate immunity against C. trachomatis is compromised without cGAS-STING signaling. We evaluated the impact of type-I interferon signaling on C. trachomatis infection in the female genital tract. Our results showed that mice lacking the type-I interferon receptor (IFN alpha R1) had significantly higher levels of live chlamydial organisms on days 3 and 5, demonstrating the protective role of type-I interferon signaling in preventing C. trachomatis infection in the mouse genital tract.