- Title
- Neonatal chlamydial infection induces mixed T-cell responses that drive allergic airway disease
- Creator
- Horvat, Jay C.; Beagley, Kenneth W.; Wade, Margaret A.; Preston, Julie A.; Hansbro, Nicole G.; Hickey, Danica K.; Kaiko, Gerard E.; Gibson, Peter G.; Foster, Paul S.; Hansbro, Philip M.
- Relation
- NHMRC.401238, NHMRC.224207 & ARC.0559210
- Relation
- American Journal of Respiratory and Critical Care Medicine Vol. 176, Issue 6, p. 556-564
- Publisher Link
- http://dx.doi.org/10.1164/rccm.200607-1005OC
- Publisher
- American Thoracic Society
- Resource Type
- journal article
- Date
- 2007
- Description
- 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.
- Subject
- asthma; infection; immunity; <i>Chlamydia</i>; T-cells
- Identifier
- http://hdl.handle.net/1959.13/1310906
- Identifier
- uon:22114
- Identifier
- ISSN:1073-449X
- Language
- eng
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