Distinct roles of CD28- and CD40 ligand-mediated costimulation in the development of protective immunity and pathology during Chlamydia muridarum urogenital infection in mice

Lili Chen, Wen Cheng, Pooja Shivshankar, Lei Lei, Xiaoyun Zhang, Yimou Wu, I. Tien Yeh, Guangming Zhong

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Infection with Chlamydia muridarum in the mouse urogenital tract can induce both protective immunity and inflammatory pathologies, which has been used as a model for understanding the immune and pathogenic mechanisms of C. trachomatis infection. We compared the roles of CD28- and CD40 ligand (CD40L)-mediated costimulation in C. muridarum infection. Mice with CD28 or CD80/CD86 gene knockout (KO) displayed an infection course similar to that of wild-type mice during both primary and secondary infection, suggesting that CD28-mediated costimulation is not required for protection against C. muridarum infection. However, mice deficient in CD40L or CD40 displayed a prolonged infection course after primary or secondary infection, suggesting that CD40-CD40L costimulation plays an essential role in the development of anti-C. muridarum immunity. Interestingly, the CD28- or CD80/CD86-deficient mice displayed significantly lower levels of in-flammatory pathologies in the upper genital tracts after primary infection, although the attenuation in inflammation was no longer significant during secondary infection. However, the CD40L or CD40 KO mice developed inflammatory pathologies as severe as those in wild-type mice following either primary or secondary infection despite the obvious deficits in adaptive immunity in these KO mice. The resistance of CD28 or CD80/CD86 KO mice to chlamydial infection correlated with production of gamma interferon, while the development of inflammatory pathologies in CD40L or CD40 KO mice correlated with the production of other proinflammatory cytokines in mouse urogenital tracts during the early stages of the infection. These observations together suggest that C. muridarum-induced protective immunity and inflammatory pathologies can be mediated by distinct costimulatory signals.

Original languageEnglish (US)
Pages (from-to)3080-3089
Number of pages10
JournalInfection and immunity
Volume77
Issue number7
DOIs
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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