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

• Published in: Journal of allergy and clinical immunology Vol. 130; no. 2; pp. 489 - 495
• Main Authors: Durrani, Sandy R., MD, Montville, Daniel J., BS, Pratt, Allison S., MD, Sahu, Sanjukta, MS, DeVries, Mark K., BS, Rajamanickam, Victoria, MS, Gangnon, Ronald E., PhD, Gill, Michelle A., MD, PhD, Gern, James E., MD, Lemanske, Robert F., MD, Jackson, Daniel J., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.08.2012; Elsevier; Elsevier Limited
• Subjects: allergic; Allergies; Allergy and Immunology; Antibodies, Anti-Idiotypic - immunology; Antibodies, Anti-Idiotypic - pharmacology; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - pharmacology; Asthma; Asthma - genetics; Asthma - immunology; Asthma - virology; Basophils - metabolism; Basophils - pathology; Basophils - virology; Biological and medical sciences; Child; Children; Chronic obstructive pulmonary disease, asthma; Dendritic cells; Dendritic Cells - metabolism; Dendritic Cells - pathology; Dendritic Cells - virology; FcεRI; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Human rhinovirus; Humans; Hypersensitivity; IgE receptor; Immune response; Immune system; Immunity, Innate - genetics; Immunoglobulin E; Immunopathology; Interferon; Interferon-alpha - biosynthesis; Interferon-alpha - immunology; Interferons; Interleukins - biosynthesis; Interleukins - immunology; Leukocytes (basophilic); Male; Medical sciences; Monocytes; Monocytes - metabolism; Monocytes - pathology; Monocytes - virology; Peripheral blood mononuclear cells; Picornaviridae Infections - genetics; Picornaviridae Infections - immunology; Picornaviridae Infections - virology; plasmacytoid dendritic cells; Pneumology; Receptors, IgE - genetics; Receptors, IgE - immunology; Respiratory Sounds - genetics; Respiratory Sounds - immunology; rhinovirus; Rhinovirus - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Viral infections; Wheezing; IgE receptor; COAST; Childhood Origins of Asthma; interferon; rhinovirus; HRV; mDC; Human rhinovirus; pDC; Plasmacytoid dendritic cell; Asthma; allergic; plasmacytoid dendritic cells; FcϵRI; Myeloid dendritic cell; FcεRI; Allergy; Picornaviridae; IgE; Natural immunity; Immunology; Antigen presenting cell; FceRI; Bronchus disease; Obstructive pulmonary disease; Child; Rhinovirus; Biological receptor; Human; Lung disease; Dendritic cell; Immunopathology; Immune response; Respiratory disease; Cytokine; Virus; Affinity; Interferon
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.05.023

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.