Published ahead of print on June 28, 2007, doi:10.1164/rccm.200607-1005OC Am. J. Respir. Crit. Care Med., Volume 176, Number 6, September 2007, 556-564 A more recent version of this article appeared on September 15, 2007
Submitted on July 23, 2006 Neonatal Chlamydial Infection Induces Mixed T Cell Responses that Drive Allergic Airways DiseaseJay C Horvat1,1 School of Biomedical Sciences, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; Vaccines, Immunity, Viruses and Asthma Group, Hunter Medical Research Institute, Newcastle, NSW, Australia, 2 Vaccines, Immunity, Viruses and Asthma Group, Hunter Medical Research Institute, Newcastle, NSW, Australia; Respiratory & Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia; Respiratory & Sleep Medicine, School of Medical Practice, University of Newcastle, Newcastle, NSW, Australia, 3 School of Biomedical Sciences, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia; Vaccines, Immunity, Viruses and Asthma Group, Hunter Medical Research Institute, Newcastle, NSW, Australia; John Curtin School of Medical Research, Division of BioSciences, Australian National University, Newcastle, NSW, Australia * To whom correspondence should be addressed. E-mail: philip.hansbro{at}newcastle.edu.au.
Rationale: Chlamydial lung infection is associated with asthma in children and adults. However, how infection influences the development of immune responses that promote asthma remains unknown. Objective: To determine the effect of chlamydial infection at different ages on the development of allergic airways 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 infected and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Features of AAD and inflammation were compared with un-infected or un sensitised controls. Results: Mild Chlamydia-induced lung disease was observed 10-15 days post-infection, evidenced by increased bacterial numbers and histopathology in the lung and reduced weight gain. After 6 weeks, infection and histopathology had resolved and rate of weight gain recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from T helper-cells and 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-T helper-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 airways 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-1/2 T cell response to antigen, which differentially affects the development of key features of AAD in the adult. Key words: asthma, infection, immunity, chlamydia, T cells
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