Distinct Roles of CD28- and CD40 Ligand-Mediated Costimulation in the Development of Protective Immunity and Pathology during Chlamydia muridarum Urogenital Infection in Mice

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)...

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Bibliographic Details
Published in:Infection and Immunity 2009-07, Vol.77 (7), p.3080-3089
Main Authors: Chen, Lili, Cheng, Wen, Shivshankar, Pooja, Lei, Lei, Zhang, Xiaoyun, Wu, Yimou, Yeh, I. Tien, Zhong, Guangming
Format: Article
Language:English
Subjects:
Animal models
Animals
B7-2 Antigen - immunology
Biological and medical sciences
CD28 antigen
CD28 Antigens - immunology
CD40 antigen
CD40 Ligand - deficiency
CD40 Ligand - immunology
CD40L protein
CD80 antigen
CD86 antigen
Chlamydia
Chlamydia Infections - immunology
Chlamydia Infections - pathology
Chlamydia muridarum - immunology
Cytokines - immunology
Female
Fundamental and applied biological sciences. Psychology
g-Interferon
Genital tract
Host Response and Inflammation
Immunity
Inflammation
Mice
Mice, Knockout
Microbiology
Secondary infection
Urinary Tract Infections - immunology
Urinary Tract Infections - microbiology
Urinary Tract Infections - pathology
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Summary: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 inflammatory 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.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00611-08