Abstract
It is widely accepted that T helper type 1 (TH1) cytokines such as interferon-γ (IFN-γ) antagonize allergic diseases mediated by TH2 cytokines. The 'hygiene hypothesis' has also proposed that decreased childhood exposure to pathogen-derived TH1 cytokines may underlie the recent increased prevalence of asthma, a TH2-mediated disease. We show here that influenza A viral infection, which induces large amounts of intrapulmonary IFN-γ production, unexpectedly enhanced later allergen-specific asthma and promoted dual allergen–specific TH1 and TH2 responses. Pulmonary dendritic cells obtained from the lung after viral clearance and resolution of acute inflammation conferred enhanced allergic disease and concurrent TH1 and TH2 immune responses, and these effects were dependent on IFN-γ secreted during the acute viral infection. Thus, respiratory viral infection and the acute TH1 response can positively regulate TH2-dependent allergic pulmonary disease in vivo, at least in part, by altering pulmonary dendritic cell function.
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Acknowledgements
We thank P. Doherty (University of Melbourne, Victoria, Australia) for providing the stocks of influenza A virus and control allantoic fluid; and M. Khan and E. Adams for technical assistance. Supported by the National Institutes of Health grant RO1 AI-44699, the American Lung Association grant RT-017-N, and the Allergy Foundation of America.
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Dahl, M., Dabbagh, K., Liggitt, D. et al. Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells. Nat Immunol 5, 337–343 (2004). https://doi.org/10.1038/ni1041
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DOI: https://doi.org/10.1038/ni1041
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