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¹ Division of Allergy and Immunology, ² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and ³ Department of Cell Biology, Washington University School of Medicine, Saint Louis, MO 63110

CORRESPONDENCE Mitchell H. Grayson:wheeze{at}allergist.com

Respiratory viral infections are associated with an increased risk of asthma, but how acute Th1 antiviral immune responses lead to chronic inflammatory Th2 disease remains undefined. We define a novel pathway that links transient viral infection to chronic lung disease with dendritic cell (DC) expression of the high-affinity IgE receptor (FcRI). In a mouse model of virus-induced chronic lung disease, in which Sendai virus triggered a switch to persistent mucous cell metaplasia and airway hyperreactivity after clearance of replicating virus, we found that FceRIa^–/– mice no longer developed mucous cell metaplasia. Viral infection induced IgE-independent, type I IFN receptor–dependent expression of FcRI on mouse lung DCs. Cross-linking DC FcRI resulted in the production of the T cell chemoattractant CCL28. FceRIa^–/– mice had decreased CCL28 and recruitment of IL-13–producing CD4⁺ T cells to the lung after viral infection. Transfer of wild-type DCs to FceRIa^–/– mice restored these events, whereas blockade of CCL28 inhibited mucous cell metaplasia. Therefore, lung DC expression of FcRI is part of the antiviral response that recruits CD4⁺ T cells and drives mucous cell metaplasia, thus linking antiviral responses to allergic/asthmatic Th2 responses.

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