Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol 2012 Aug;130(2):489-95
Date
07/07/2012Pubmed ID
22766097Pubmed Central ID
PMC3437329DOI
10.1016/j.jaci.2012.05.023Scopus ID
2-s2.0-84864419876 (requires institutional sign-in at Scopus site) 198 CitationsAbstract
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.
Author List
Durrani SR, Montville DJ, Pratt AS, Sahu S, DeVries MK, Rajamanickam V, Gangnon RE, Gill MA, Gern JE, Lemanske RF Jr, Jackson DJAuthor
Allison S. Remiker MD Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antibodies, Anti-IdiotypicAntibodies, Neutralizing
Asthma
Basophils
Child
Dendritic Cells
Female
Flow Cytometry
Gene Expression
Humans
Immunity, Innate
Interferon-alpha
Interferons
Interleukins
Male
Monocytes
Picornaviridae Infections
Receptors, IgE
Respiratory Sounds
Rhinovirus
