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.
Nagarajan
Uma M
UM
Division of Pediatric Infectious Diseases, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202, USA. nagarajanuma@uams.edu
Prantner
Daniel
D
Sikes
James D
JD
Andrews
Charles W
CW
Goodwin
Anna M
AM
Nagarajan
Shanmugam
S
Darville
Toni
T
D000818:Animals; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D054370:Chemokine CXCL9 / Q000096:biosynthesis; D002690:Chlamydia Infections / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology*; D015169:Colony Count, Microbial; D005260:Female; D052776:Female Urogenital Diseases / Q000382:microbiology* / Q000473:pathology*; D007370:Interferon Type I / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D013601:T-Lymphocytes / Q000276:immunology
D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta