title: Contribution of interleukin-12 p35 (IL-12p35) and IL-12p40 to protective immunity and pathology in mice infected with Chlamydia muridarum.
abstract: The p35 molecule is unique to interleukin-12 (IL-12), while p40 is shared by both IL-12 and IL-23. IL-12 promotes Th1 T cell responses, while IL-23 promotes Th17 T cell responses. The roles of IL-12p35- and IL-12p40-mediated responses in chlamydial infection were compared in mice following an intravaginal infection with Chlamydia muridarum. Mice deficient in either IL-12p35 or p40 both developed similar but prolonged infection time courses, confirming the roles of IL-12-mediated immune responses in clearing primary infection. However, all mice, regardless of genotype, cleared reinfection within 2 weeks, suggesting that an IL-12- or IL-23-independent adaptive immunity is protective against chlamydial infection. All infected mice developed severe oviduct hydrosalpinx despite the increased Th2 responses in IL-12p35- or IL-12p40-deficient mice, suggesting that Th2-dominant responses can contribute to Chlamydia-induced inflammatory pathology. Compared to IL-12p35 knockout mice, the IL-12p40-deficient mice exhibited more extensive spreading of chlamydial organisms into kidney tissues, leading to significantly increased incidence of pyelonephritis, which both confirms the role of IL-12 or IL-23-independent host responses in Chlamydia-induced pathologies and suggests that in the absence of IL-12/IFN-γ-mediated Th1 immunity, an IL-23-mediated response may play an important role in restricting chlamydial organisms from spreading into distal organs. These observations together provide important information for both understanding chlamydial pathogenesis and developing anti-Chlamydia vaccines.
authors.affiliation: Department of Pathogen Biology, University of South China, Hengyang, Hunan, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Sha
authors.initials: S
authors.lastname: Xu
authors.forename: Chunxue
authors.initials: C
authors.lastname: Lu
authors.forename: Jianlin
authors.initials: J
authors.lastname: Chen
authors.forename: Zhangsheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Gangqiu
authors.initials: G
authors.lastname: Wu
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology*; D023502:Chlamydia muridarum / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000276:immunology*; D053762:Interleukin-12 Subunit p40 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40