title: Caspase-1 contributes to Chlamydia trachomatis-induced upper urogenital tract inflammatory pathologies without affecting the course of infection.
abstract: Chlamydia trachomatis infection induces inflammatory pathologies in the upper genital tract, potentially leading to ectopic pregnancy and infertility in the affected women. Caspase-1 is required for processing and release of the inflammatory cytokines interleukin-1beta (IL-1beta), IL-18, and possibly IL-33. In the present study, we evaluated the role of caspase-1 in chlamydial infection and pathogenesis. Although chlamydial infection induced caspase-1 activation and processing of IL-1beta, mice competent and mice deficient in caspase-1 experienced similar courses of chlamydial infection in their urogenital tracts, suggesting that Chlamydia-activated caspase-1 did not play a significant role in resolution of chlamydial infection. However, when genital tract tissue pathologies were examined, the caspase-1-deficient mice displayed much reduced inflammatory damage. The reduction in inflammation was most obvious in the fallopian tube tissue. These observations demonstrated that although caspase-1 is not required for controlling chlamydial infection, caspase-1-mediated responses can exacerbate the Chlamydia-induced inflammatory pathologies in the upper genital tract, suggesting that the host caspase-1 may be targeted for selectively attenuating chlamydial pathogenicity without affecting the host defense against chlamydial infection.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.forename: Pooja
authors.initials: P
authors.lastname: Shivshankar
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000172:deficiency / Q000502:physiology*; D002460:Cell Line; D002690:Chlamydia Infections / Q000473:pathology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D005187:Fallopian Tubes / Q000473:pathology; D005260:Female; D005836:Genitalia, Female / Q000382:microbiology* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D014599:Uterus / Q000473:pathology
chemical_list: D020170:Caspase 1