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

Sandy R. Durrani, Daniel J. Montville, Allison S. Pratt, Sanjukta Sahu, Mark K. Devries, Victoria Rajamanickam, Ronald E. Gangnon, Michelle A. Gill, James E. Gern, Robert F. Lemanske, Daniel J. Jackson

Research output: Contribution to journalArticle

114 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)489-495
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume130
Issue number2
DOIs
StatePublished - Aug 2012

Fingerprint

IgE Receptors
Rhinovirus
Innate Immunity
Dendritic Cells
Asthma
Respiratory Sounds
Myeloid Cells
Basophils
Monocytes
Flow Cytometry
Hypersensitivity
Rabbits

Keywords

  • allergic
  • Asthma
  • FcεRI
  • IgE receptor
  • interferon
  • plasmacytoid dendritic cells
  • rhinovirus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Durrani, S. R., Montville, D. J., Pratt, A. S., Sahu, S., Devries, M. K., Rajamanickam, V., ... Jackson, D. J. (2012). Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. Journal of Allergy and Clinical Immunology, 130(2), 489-495. https://doi.org/10.1016/j.jaci.2012.05.023

Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. / Durrani, Sandy R.; Montville, Daniel J.; Pratt, Allison S.; Sahu, Sanjukta; Devries, Mark K.; Rajamanickam, Victoria; Gangnon, Ronald E.; Gill, Michelle A.; Gern, James E.; Lemanske, Robert F.; Jackson, Daniel J.

In: Journal of Allergy and Clinical Immunology, Vol. 130, No. 2, 08.2012, p. 489-495.

Research output: Contribution to journalArticle

Durrani, SR, Montville, DJ, Pratt, AS, Sahu, S, Devries, MK, Rajamanickam, V, Gangnon, RE, Gill, MA, Gern, JE, Lemanske, RF & Jackson, DJ 2012, 'Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children', Journal of Allergy and Clinical Immunology, vol. 130, no. 2, pp. 489-495. https://doi.org/10.1016/j.jaci.2012.05.023
Durrani, Sandy R. ; Montville, Daniel J. ; Pratt, Allison S. ; Sahu, Sanjukta ; Devries, Mark K. ; Rajamanickam, Victoria ; Gangnon, Ronald E. ; Gill, Michelle A. ; Gern, James E. ; Lemanske, Robert F. ; Jackson, Daniel J. / Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. In: Journal of Allergy and Clinical Immunology. 2012 ; Vol. 130, No. 2. pp. 489-495.
@article{0be52007557f4c40871cf07573510aaf,
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.",
keywords = "allergic, Asthma, FcεRI, IgE receptor, interferon, plasmacytoid dendritic cells, rhinovirus",
author = "Durrani, {Sandy R.} and Montville, {Daniel J.} and Pratt, {Allison S.} and Sanjukta Sahu and Devries, {Mark K.} and Victoria Rajamanickam and Gangnon, {Ronald E.} and Gill, {Michelle A.} and Gern, {James E.} and Lemanske, {Robert F.} and Jackson, {Daniel J.}",
year = "2012",
month = "8",
doi = "10.1016/j.jaci.2012.05.023",
language = "English (US)",
volume = "130",
pages = "489--495",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children

AU - Durrani, Sandy R.

AU - Montville, Daniel J.

AU - Pratt, Allison S.

AU - Sahu, Sanjukta

AU - Devries, Mark K.

AU - Rajamanickam, Victoria

AU - Gangnon, Ronald E.

AU - Gill, Michelle A.

AU - Gern, James E.

AU - Lemanske, Robert F.

AU - Jackson, Daniel J.

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

KW - allergic

KW - Asthma

KW - FcεRI

KW - IgE receptor

KW - interferon

KW - plasmacytoid dendritic cells

KW - rhinovirus

UR - http://www.scopus.com/inward/record.url?scp=84864419876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864419876&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2012.05.023

DO - 10.1016/j.jaci.2012.05.023

M3 - Article

VL - 130

SP - 489

EP - 495

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 2

ER -