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

Nat Immunol. 2004 Mar;5(3):337-43. doi: 10.1038/ni1041. Epub 2004 Feb 15.


It is widely accepted that T helper type 1 (T(H)1) cytokines such as interferon-gamma (IFN-gamma) antagonize allergic diseases mediated by T(H)2 cytokines. The 'hygiene hypothesis' has also proposed that decreased childhood exposure to pathogen-derived T(H)1 cytokines may underlie the recent increased prevalence of asthma, a T(H)2-mediated disease. We show here that influenza A viral infection, which induces large amounts of intrapulmonary IFN-gamma production, unexpectedly enhanced later allergen-specific asthma and promoted dual allergen-specific T(H)1 and T(H)2 responses. Pulmonary dendritic cells obtained from the lung after viral clearance and resolution of acute inflammation conferred enhanced allergic disease and concurrent T(H)1 and T(H)2 immune responses, and these effects were dependent on IFN-gamma secreted during the acute viral infection. Thus, respiratory viral infection and the acute T(H)1 response can positively regulate T(H)2-dependent allergic pulmonary disease in vivo, at least in part, by altering pulmonary dendritic cell function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Influenza A virus
  • Interferon-gamma / physiology
  • Lung / cytology
  • Lung / immunology*
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / complications
  • Orthomyxoviridae Infections / immunology*
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology


  • Interferon-gamma