Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children

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 (Fc epsilon RI) 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 Fc epsilon RI 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 Fc epsilon RI, followed by stimulation with HRV-16, and IFN-alpha and IFN-lambda 1 production was measured by Luminex. The relationships among Fc epsilon RI expression and cross-linking, HRV-induced IFN-alpha and IFN-lambda 1 production, and childhood allergy and asthma were subsequently analyzed. Results: Fc epsilon RI alpha expression on pDCs was inversely associated with HRV-induced IFN-alpha and IFN-lambda 1 production. Cross-linking Fc epsilon RI before HRV stimulation further reduced PBMC IFN-alpha (47% relative reduction; 95% CI, 32% to 62%; P < .0001) and IFN-lambda 1 ( 81% relative reduction; 95% CI, 69% to 93%; P < .0001) secretion. Allergic asthmatic children had higher surface expression of Fc epsilon RIa on pDCs and myeloid dendritic cells when compared with that seen in nonallergic nonasthmatic children. Furthermore, after Fc epsilon RI cross-linking, allergic asthmatic children had significantly lower HRV-induced IFN responses than allergic nonasthmatic children (IFN-alpha, P = .004; IFN-lambda 1, P = .02) and nonallergic nonasthmatic children ( IFN-alpha, P = .002; IFN-lambda 1, P = .01). Conclusions: Allergic asthmatic children have impaired innate immune responses to HRV that correlate with increased Fc epsilon RI expression on pDCs and are reduced by Fc epsilon RI cross-linking. These effects likely increase susceptibility to HRV-induced wheezing and asthma exacerbations. (J Allergy Clin Immunol 2012; 130:489-95.)