IL-1α Is Essential for Oviduct Pathology during Genital Chlamydial Infection in Mice.

Chlamydia trachomatis infection of the female genital tract can lead to irreversible fallopian tube scarring. In the mouse model of genital infection using Chlamydia muridarum, IL-1R signaling plays a critical role in oviduct tissue damage. In this study, we investigated the pathologic role of IL-1α, one of the two proinflammatory cytokines that bind to IL-1R. Il1a-/- mice infected with C. muridarum cleared infection at their cervix at the same rate as wild-type (WT) mice, but were significantly protected from end point oviduct damage and fibrosis. The contribution of IL-1α to oviduct pathology was more dramatic than observed in mice deficient for IL-1β. Although chlamydial burden was similar in WT and Il1a-/- oviduct during peak days of infection, levels of IL-1β, IL-6, CSF3, and CXCL2 were reduced in Il1a-/- oviduct lysates. During infection, Il1a-/- oviducts and uterine horns exhibited reduced neutrophil infiltration, and this reduction persisted after the infection resolved. The absence of IL-1α did not compromise CD4 T cell recruitment or function during primary or secondary chlamydial infection. IL-1α is expressed predominantly by luminal cells of the genital tract in response to infection, and low levels of expression persisted after the infection cleared. Ab-mediated depletion of IL-1α in WT mice prevented infection-induced oviduct damage, further supporting a key role for IL-1α in oviduct pathology. Copyright © 2020 by The American Association of Immunologists, Inc.

Citation

Clare E Gyorke, Avinash Kollipara, John Allen, Yugen Zhang, J Ashley Ezzell, Toni Darville, Stephanie A Montgomery, Uma M Nagarajan. IL-1α Is Essential for Oviduct Pathology during Genital Chlamydial Infection in Mice. Journal of immunology (Baltimore, Md. : 1950). 2020 Dec 01;205(11):3037-3049

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PMID: 33087404

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