August 2005, VOLUME116 /ISSUE Supplement 2

Viral-Induced T Helper Type 1 Responses Enhance Allergic Disease by Effects on Lung Dendritic Cells

  1. Akaluck Thatayatikom, MD
  1. St Louis, MO
  1. Andrew H. Liu, MD
  1. Denver, CO

Dahl ME, Dabbagh K, Liggitt D, Kim S, Lewis DB. Nat Immunol. 2004;5:337–343

Purpose of the Study.

To determine the role of interferon (IFN)-γ and dendritic cells in allergic pulmonary disease after influenza A infection.

Study Population.

IFN-γ knockout and wild-type mice completely recovered from influenza A infection were studied.


Mice were inoculated intranasally with influenza A virus. The postinfluenza mice were then sensitized and challenged with allergen. Airway inflammatory cells, specific antibody responses, and pulmonary dendritic cell functions were examined. In some of the wild-type mice, a neutralizing IFN-γ monoclonal antibody was administered repeatedly after the viral inoculation.


Pulmonary dendritic cells of postinfluenza mice enhanced allergen-specific T-helper (Th)2 responses via an IFN-γ-dependent mechanism.


The Th1 immune response caused by an influenza infection perpetuates Th2-dependent allergic asthma by altering pulmonary dendritic cell function.

Reviewers’ Comments.

The role of respiratory viral infections in the development of allergen sensitization and asthma has been perplexing. Acute viral respiratory tract infections are the primary cause of asthma exacerbations in children and adults; however, the influence of viral respiratory infections on subsequent allergic sensitization and disease in young children is unclear. Viral infections are simplistically thought to augment Th1 (interleukin [IL]-12 and IFN-γ) responses and, as a result, antagonize Th2 (IL-4, IL-5, and IL-13) responses and decrease the risk of developing atopic diseases and asthma (ie, the hygiene hypothesis). Based on mouse models of allergic asthma, the impact of influenza infection on Th2 development and allergen sensitization has resulted in both beneficial and detrimental outcomes. The factors accounting for the different results are likely to be differences in experimental methods, including the timing of infections relative to allergen sensitization, the type and dose of allergen used, and the strain of the mouse. The findings of the Dahl et al study indicate that a preceding influenza infection with subsequent Th1 immune responses can amplify subsequent Th2 immunity. Thus, the Th1-Th2 paradigm of mutual exclusivity (ie, Th1 inhibits Th2, and vice versa) seems to be overly simplistic in the circumstance in which Th1 begets Th2. Although the result of the study has not been observed or correlated in humans, the finding may provide a mechanistic explanation for a recent report of the increased risk of asthma/reactive airways disease in young children <36 months of age who received a live attenuated intranasal influenza vaccine (published by Bergen et al in Pediatr Infect Dis J. 2004;23:138-144).