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

J Immunol. 2020 Dec 1;205(11):3037-3049. doi: 10.4049/jimmunol.2000600. Epub 2020 Oct 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Cervix Uteri / metabolism
  • Cervix Uteri / microbiology
  • Chlamydia Infections / metabolism*
  • Chlamydia Infections / microbiology
  • Chlamydia muridarum / pathogenicity
  • Disease Models, Animal
  • Female
  • Genitalia, Female / metabolism*
  • Genitalia, Female / microbiology
  • Interleukin-1alpha / metabolism*
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / physiology
  • Oviducts / metabolism*
  • Oviducts / microbiology
  • Reproductive Tract Infections / metabolism
  • Reproductive Tract Infections / microbiology


  • Il1a protein, mouse
  • Interleukin-1alpha
  • Interleukin-1beta