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Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children.
J Allergy Clin Immunol 2012; 130(2):489-95JA

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+Show Affiliations

Department of Medicine, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI 53792-9988, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22766097

Citation

Durrani, Sandy R., et al. "Innate Immune Responses to Rhinovirus Are Reduced By the High-affinity IgE Receptor in Allergic Asthmatic Children." The Journal of Allergy and Clinical Immunology, vol. 130, no. 2, 2012, pp. 489-95.
Durrani SR, Montville DJ, Pratt AS, et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol. 2012;130(2):489-95.
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. The Journal of Allergy and Clinical Immunology, 130(2), pp. 489-95. doi:10.1016/j.jaci.2012.05.023.
Durrani SR, et al. Innate Immune Responses to Rhinovirus Are Reduced By the High-affinity IgE Receptor in Allergic Asthmatic Children. J Allergy Clin Immunol. 2012;130(2):489-95. PubMed PMID: 22766097.
* Article titles in AMA citation format should be in sentence-case
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,Jr AU - Jackson,Daniel J, Y1 - 2012/07/04/ PY - 2012/03/23/received PY - 2012/05/16/revised PY - 2012/05/18/accepted PY - 2012/7/7/entrez PY - 2012/7/7/pubmed PY - 2012/10/18/medline SP - 489 EP - 95 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 130 IS - 2 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/22766097/Innate_immune_responses_to_rhinovirus_are_reduced_by_the_high_affinity_IgE_receptor_in_allergic_asthmatic_children_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(12)00861-5 DB - PRIME DP - Unbound Medicine ER -