Contribution of interleukin-12 p35 (il-12p35) and il-12p40 to protective immunity and pathology in mice infected with chlamydia muridarum

Lili Chen, Lei Lei, Zhou Zhou, Jie He, Sha Xu, Chunxue Lu, Jianlin Chen, Zhangsheng Yang, Gangqiu Wu, I. Tien Yeh, Guangming Zhong, Yimou Wu

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2962-2971
Number of pages10
JournalInfection and immunity
Volume81
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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