Type I Interferon Signaling Exacerbates Chlamydia muridarum Genital Infection in a Murine Model

• Published in: Infection and Immunity Vol. 76; no. 10; pp. 4642 - 4648
• Main Authors: Nagarajan, Uma M, Prantner, Daniel, Sikes, James D, Andrews, Charles W. Jr, Goodwin, Anna M, Nagarajan, Shanmugam, Darville, Toni
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.10.2008; American Society for Microbiology (ASM)
• Subjects: Animals; Bacterial Infections; Biological and medical sciences; Chemokine CXCL10 - biosynthesis; Chemokine CXCL9 - biosynthesis; Chlamydia; Chlamydia Infections - immunology; Chlamydia muridarum - immunology; Colony Count, Microbial; Female; Female Urogenital Diseases - microbiology; Female Urogenital Diseases - pathology; Fundamental and applied biological sciences. Psychology; Interferon Type I - immunology; Lymph Nodes - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Receptor, Interferon alpha-beta - deficiency; T-Lymphocytes - immunology; Infection; Animal model; Microbiology; Cytokine; Bacteriosis; Chlamydiosis; Interferon; Immunity
• DOI: 10.1128/IAI.00629-08
• ISSN: 0019-9567

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.