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Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells

Nature Immunology volume 5, pages 337–343 (2004)Cite this article

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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Figure 1: Influenza A viral infection enhances subsequent allergen-induced inflammation and allergen-specific antibody in an IFN-γ-dependent way.
Figure 2: Influenza A viral infection leads to persistent formation of bronchus-associated lymphoid tissue and increased numbers of lung DCs at day 30 after inoculation.
Figure 3: Influenza A viral infection alters the number and phenotype of lung DCs.
Figure 4: IFN-γ mediates the effects of influenza infection on lung DC numbers and phenotype.
Figure 5: Lung DCs from post-flu mice have an enhanced capacity to promote CD4+ T cell activation and differentiation and to secrete IL-12.
Figure 6: Adoptive transfer of OVA-pulsed lung DCs from post-flu mice enhances allergic inflammation and allergen-specific IgG2a.
Figure 7: IFN-γ produced during acute viral infection acts on lung DCs to enhance their function in vivo.

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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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Author notes

  1. Karim Dabbagh

    Present address: Roche Palo Alto, Palo Alto, California, 94304, USA

  2. Martin E Dahl and Karim Dabbagh: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics and the Immunology Program, Stanford University School of Medicine, Stanford, 94305, California, USA

    Martin E Dahl, Karim Dabbagh, Sung Kim & David B Lewis

  2. Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, 98195, Washington, USA

    Denny Liggitt

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Correspondence to David B Lewis.

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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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