BACKGROUND: Children with allergic asthma have more frequent and severe human rhinovirus (HRV)-induced wheezing and asthma exacerbations through unclear mechanisms. OBJECTIVE: We sought to determine whether increased high-affinity IgE receptor (FcepsilonRI) expression and cross-linking impairs innate immune responses to HRV, particularly in allergic asthmatic children. METHODS: PBMCs were obtained from 44 children, and surface expression of FcepsilonRI on plasmacytoid dendritic cells (pDCs), myeloid dendritic cells, monocytes, and basophils was assessed by using flow cytometry. Cells were also incubated with rabbit anti-human IgE to cross-link FcepsilonRI, followed by stimulation with HRV-16, and IFN-alpha and IFN-lambda1 production was measured by Luminex. The relationships among FcepsilonRI expression and cross-linking, HRV-induced IFN-alpha and IFN-lambda1 production, and childhood allergy and asthma were subsequently analyzed. RESULTS: FcepsilonRIalpha expression on pDCs was inversely associated with HRV-induced IFN-alpha and IFN-lambda1 production. Cross-linking FcepsilonRI before HRV stimulation further reduced PBMC IFN-alpha (47% relative reduction; 95% CI, 32% to 62%; P< .0001) and IFN-lambda1 (81% relative reduction; 95% CI, 69% to 93%; P< .0001) secretion. Allergic asthmatic children had higher surface expression of FcepsilonRIalpha on pDCs and myeloid dendritic cells when compared with that seen in nonallergic nonasthmatic children. Furthermore, after FcepsilonRI cross-linking, allergic asthmatic children had significantly lower HRV-induced IFN responses than allergic nonasthmatic children (IFN-alpha, P= .004; IFN-lambda1, P= .02) and nonallergic nonasthmatic children (IFN-alpha, P= .002; IFN-lambda1, P= .01). CONCLUSIONS: Allergic asthmatic children have impaired innate immune responses to HRV that correlate with increased FcepsilonRI expression on pDCs and are reduced by FcepsilonRI cross-linking. These effects likely increase susceptibility to HRV-induced wheezing and asthma exacerbations.