Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology

Horvat, Jay C., Starkey, Malcolm R., Kim, Richard Y., Phipps, Simon, Gibson, Peter G., Beagley, Kenneth W., Foster, Paul S. and Hansbro, Philip M. (2010) Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology. Journal of Allergy and Clinical Immunology, 125 3: 617-625.e6. doi:10.1016/j.jaci.2009.10.018

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Author Horvat, Jay C.
Starkey, Malcolm R.
Kim, Richard Y.
Phipps, Simon
Gibson, Peter G.
Beagley, Kenneth W.
Foster, Paul S.
Hansbro, Philip M.
Title Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology
Journal name Journal of Allergy and Clinical Immunology   Check publisher's open access policy
ISSN 0091-6749
1085-8725
1097-6825
Publication date 2010-03
Sub-type Article (original research)
DOI 10.1016/j.jaci.2009.10.018
Volume 125
Issue 3
Start page 617
End page 625.e6
Total pages 9
Place of publication Philadelphia, PA, U.S.A.
Publisher Mosby
Collection year 2011
Language eng
Formatted abstract
Background
Asthma typically originates in early-life, and the impact of infection during immunologic maturation is a critical factor in disease pathogenesis. The progression of aberrant TH2 cell responses and disease development has been attributed to a lack of infections. However, exposure to specific pathogens such as Chlamydia may alter immunologic programming and predispose to asthma.
Objective
To investigate the effects of chlamydial infection at different ages on allergic airways disease in later life.
Methods
Neonatal, infant, or adult BALB/c mice were infected and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Hallmark features of allergic airways disease were compared with uninfected allergic and nonallergic controls.
Results
Early-life (neonatal and infant) but not adult chlamydial infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease. Notably early-life infection increased mucus-secreting cell numbers, IL-13 expression, and airway hyperresponsiveness. Neonatal infection attenuated eosinophil influx and ovalbumin-specific TH2 cytokine release and numbers of activated myeloid dendritic cells (DCs) in lymph nodes. By contrast, infant infection augmented features of allergic inflammation with increased airway eosinophils, TH2 cytokine, and DC responses. Both neonatal and infant infection increased systemic DC-induced IL-13 release from CD4+ T cells. The timing of infection had significant effects on lung structure because neonatal but not infant or adult infection induced increases in alveolar diameter.
Conclusion
Early-life respiratory chlamydial infections modulate immune responses, alter lung function and structure, and enhance the severity of allergic airways disease in later life.
© 2010 American Academy of Allergy, Asthma & Immunology
Keyword Asthma
Chlamydia
immunologic programming
lung structure
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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Created: Wed, 09 Mar 2011, 14:29:18 EST