STING agonists reduce genital chlamydial infection and attenuate inflammation and pathology.

The cGAS-STING pathway is activated during chlamydial infection and plays a critical role in controlling Chlamydia trachomatis infection in the mouse lower genital tract. The current study evaluated whether intravaginal administration of exogenous STING agonists could inhibit chlamydial infection and attenuate upper genital tract pathologies in a mouse model of Chlamydia muridarum infection. We found that both the STING agonists 2'3'-cGAMP and diABZI significantly reduced the shedding of live chlamydial organisms recovered from the vaginal swabs and markedly decreased hydrosalpinx and inflammatory infiltrates induced by C. muridarum, which are major pathological outcomes associated with tubal infertility in women infected with C. trachomatis. Importantly, mice exhibited local and systemic tolerance to the STING agonists. Collectively, these findings suggest a novel STING agonist-based approach for controlling chlamydial infection, which could offer a non-antibiotic, mucosally targeted strategy to reduce the risk of hydrosalpinx in exposed women.