Type I interferon signaling exacerbates Chlamydia muridarum genital infection in a murine model.

Type I interferons (IFNs) induced during in vitro chlamydial infection exert bactericidal and immunomodulatory functions. To determine the precise role of type I IFNs during in vivo chlamydial genital infection, we examined the course and outcome of Chlamydia muridarum genital infection in mice genetically deficient in the receptor for type I IFNs (IFNAR(-/-) mice). A significant reduction in chlamydial shedding and duration of lower genital tract infection was observed in IFNAR(-/-) mice in comparison to the level of chlamydial shedding and duration of infection in wild-type (WT) mice. Furthermore, IFNAR(-/-) mice developed less chronic oviduct pathology in comparison to that in WT mice. Compared to the WT, IFNAR(-/-) mice had a greater number of chlamydial-specific T cells in their iliac lymph nodes 21 days postinfection. IFNAR(-/-) mice also exhibited earlier and enhanced CD4 T-cell recruitment to the cervical tissues, which was associated with increased expression of CXCL9 in the genital secretions of IFNAR(-/-) mice, but not with expression of CXCL10, which was reduced in the genital secretions of IFNAR(-/-) mice. These data suggest that type I IFNs exacerbate C. muridarum genital infection through an inhibition of the chlamydial-specific CD4 T-cell response.