Neonatal chlamydial infection induces mixed T-cell responses that drive allergic airway disease.
2007
Horvat, JC | Beagley, KW | Wade, MA | Preston, JA | Hansbro, NG | Hickey, DK | Kaiko, GE | Gibson, PG | Foster, PS | Hansbro, PM
RATIONALE: Chlamydial lung infection has been associated with asthma in children and adults. However, how chlamydial infection influences the development of immune responses that promote asthma remains unknown. OBJECTIVES: To determine the effect of chlamydial infection at various ages on the development of allergic airway disease (AAD). METHODS: Mouse models of chlamydial lung infection and ovalbumin-induced AAD were established in neonatal and adult BALB/c mice. Neonatal or adult mice were given a chlamydial infection and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Features of AAD and inflammation were compared between uninfected or unsensitized controls. MEASUREMENTS AND MAIN RESULTS: Mild Chlamydia-induced lung disease was observed 10-15 days after infection, as evidenced by increased bacterial numbers and histopathology in the lung and a reduction in weight gain. After 6 weeks, infection and histopathology had resolved and the rate of weight gain had recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from helper T cells and by the numbers of eosinophils recruited to the lung in response to ovalbumin exposure. Remarkably, the effects of early-life infection were associated with the generation of both type 1 and 2 ovalbumin-specific helper T-cell cytokine and antibody responses. Furthermore, although neonatal infection significantly attenuated eosinophilia, the generation of the mixed T-cell response exacerbated other hallmark features of asthma: mucus hypersecretion and airway hyperresponsiveness. Moreover, infection prolonged the expression of AAD and these effects were restricted to early-life infection. CONCLUSIONS: Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.
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