title: Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children.
abstract: 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 (FcεRI) 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 FcεRI 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 FcεRI, followed by stimulation with HRV-16, and IFN-α and IFN-λ1 production was measured by Luminex. The relationships among FcεRI expression and cross-linking, HRV-induced IFN-α and IFN-λ1 production, and childhood allergy and asthma were subsequently analyzed.
  
  
  RESULTS
  FcεRIα expression on pDCs was inversely associated with HRV-induced IFN-α and IFN-λ1 production. Cross-linking FcεRI before HRV stimulation further reduced PBMC IFN-α (47% relative reduction; 95% CI, 32% to 62%; P< .0001) and IFN-λ1 (81% relative reduction; 95% CI, 69% to 93%; P< .0001) secretion. Allergic asthmatic children had higher surface expression of FcεRIα on pDCs and myeloid dendritic cells when compared with that seen in nonallergic nonasthmatic children. Furthermore, after FcεRI cross-linking, allergic asthmatic children had significantly lower HRV-induced IFN responses than allergic nonasthmatic children (IFN-α, P= .004; IFN-λ1, P= .02) and nonallergic nonasthmatic children (IFN-α, P= .002; IFN-λ1, P= .01).
  
  
  CONCLUSIONS
  Allergic asthmatic children have impaired innate immune responses to HRV that correlate with increased FcεRI expression on pDCs and are reduced by FcεRI cross-linking. These effects likely increase susceptibility to HRV-induced wheezing and asthma exacerbations.
authors: Department of Medicine, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI 53792-9988, USA.
authors: Sandy R
authors: SR
authors: Durrani
authors: Daniel J
authors: DJ
authors: Montville
authors: Allison S
authors: AS
authors: Pratt
authors: Sanjukta
authors: S
authors: Sahu
authors: Mark K
authors: MK
authors: DeVries
authors: Victoria
authors: V
authors: Rajamanickam
authors: Ronald E
authors: RE
authors: Gangnon
authors: Michelle A
authors: MA
authors: Gill
authors: James E
authors: JE
authors: Gern
authors: Robert F
authors: RF
authors: Lemanske
authors: Daniel J
authors: DJ
authors: Jackson
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000821:virology; D001491:Basophils / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002648:Child; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D007372:Interferons; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D010850:Picornaviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D012135:Respiratory Sounds / Q000235:genetics / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology; D000095022:Interferon Lambda
chemical_list: D000888:Antibodies, Anti-Idiotypic; D057134:Antibodies, Neutralizing; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D017455:Receptors, IgE; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C026408:anti-IgE antibodies