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Rhinovirus 16-induced IFN-α and IFN-β are deficient in bronchoalveolar lavage cells in asthmatic patients.
J Allergy Clin Immunol 2012; 129(6):1506-1514.e6JA

Abstract

BACKGROUND

Asthmatic patients have defective rhinovirus-induced IFN-β and IFN-λ production from bronchial epithelial cells and IFN-λ from bronchoalveolar lavage (BAL) cells. Whether bronchoalveolar lavage cells have defective type I interferon responses to rhinovirus is unknown, as are mechanisms explaining defective rhinovirus interferon induction in asthmatic patients.

OBJECTIVE

We sought to investigate rhinovirus induction of type I interferons in BAL and blood mononuclear cells from asthmatic patients and healthy subjects and to investigate mechanisms of any deficiency observed.

METHODS

BAL and blood mononuclear cells from atopic asthmatic patients and healthy subjects were infected with rhinovirus ex vivo. Interferon proteins were analyzed by using ELISA. mRNA expression of key components of interferon induction pathways were analyzed by using quantitative PCR.

RESULTS

Rhinovirus induction of type I interferon protein was delayed and deficient in BAL cells from asthmatic patients, and lower interferon levels were associated with greater airway hyperresponsiveness and skin prick test response positivity. Expression of Toll-like receptor (TLR) 3, TLR7, TLR8, retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA-5), TIR domain-containing adapter-inducing IFN-β (TRIF), myeloid differentiation primary response gene 88 (MyD88), caspase recruitment domain adaptor inducing IFN-β (CARDIF), IL-1 receptor-associated kinase 4 (IRAK4), IκB kinase β (IKKB), IκB kinase ι (IKKI), interferon regulatory factors 3 and 7, and rhinovirus induction of expression of the virus-inducible molecules TLR3, TLR7, RIG-I, and MDA-5 were not impaired in these interferon-deficient BAL cells in asthmatic patients. Defective rhinovirus interferon induction was not observed in blood mononuclear cells.

CONCLUSIONS

Rhinovirus induction of type I interferons in BAL cells is delayed and deficient and might be a marker of more severe asthma. Defective rhinovirus interferon induction in asthmatic patients was not accompanied by differences in the expression or induction of key molecules implicated in viral induction of interferons.

Authors+Show Affiliations

National Heart & Lung Institute, Imperial College London, London, United Kingdom. annemarie.sykes@imperial.ac.ukNo 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, Non-U.S. Gov't

Language

eng

PubMed ID

22657407

Citation

Sykes, Annemarie, et al. "Rhinovirus 16-induced IFN-α and IFN-β Are Deficient in Bronchoalveolar Lavage Cells in Asthmatic Patients." The Journal of Allergy and Clinical Immunology, vol. 129, no. 6, 2012, pp. 1506-1514.e6.
Sykes A, Edwards MR, Macintyre J, et al. Rhinovirus 16-induced IFN-α and IFN-β are deficient in bronchoalveolar lavage cells in asthmatic patients. J Allergy Clin Immunol. 2012;129(6):1506-1514.e6.
Sykes, A., Edwards, M. R., Macintyre, J., del Rosario, A., Bakhsoliani, E., Trujillo-Torralbo, M. B., ... Johnston, S. L. (2012). Rhinovirus 16-induced IFN-α and IFN-β are deficient in bronchoalveolar lavage cells in asthmatic patients. The Journal of Allergy and Clinical Immunology, 129(6), pp. 1506-1514.e6. doi:10.1016/j.jaci.2012.03.044.
Sykes A, et al. Rhinovirus 16-induced IFN-α and IFN-β Are Deficient in Bronchoalveolar Lavage Cells in Asthmatic Patients. J Allergy Clin Immunol. 2012;129(6):1506-1514.e6. PubMed PMID: 22657407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rhinovirus 16-induced IFN-α and IFN-β are deficient in bronchoalveolar lavage cells in asthmatic patients. AU - Sykes,Annemarie, AU - Edwards,Michael R, AU - Macintyre,Jonathan, AU - del Rosario,Ajerico, AU - Bakhsoliani,Eteri, AU - Trujillo-Torralbo,Maria-Belen, AU - Kon,Onn Min, AU - Mallia,Patrick, AU - McHale,Mark, AU - Johnston,Sebastian L, PY - 2011/12/15/received PY - 2012/02/19/revised PY - 2012/03/14/accepted PY - 2012/6/5/entrez PY - 2012/6/5/pubmed PY - 2013/1/24/medline SP - 1506 EP - 1514.e6 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 129 IS - 6 N2 - BACKGROUND: Asthmatic patients have defective rhinovirus-induced IFN-β and IFN-λ production from bronchial epithelial cells and IFN-λ from bronchoalveolar lavage (BAL) cells. Whether bronchoalveolar lavage cells have defective type I interferon responses to rhinovirus is unknown, as are mechanisms explaining defective rhinovirus interferon induction in asthmatic patients. OBJECTIVE: We sought to investigate rhinovirus induction of type I interferons in BAL and blood mononuclear cells from asthmatic patients and healthy subjects and to investigate mechanisms of any deficiency observed. METHODS: BAL and blood mononuclear cells from atopic asthmatic patients and healthy subjects were infected with rhinovirus ex vivo. Interferon proteins were analyzed by using ELISA. mRNA expression of key components of interferon induction pathways were analyzed by using quantitative PCR. RESULTS: Rhinovirus induction of type I interferon protein was delayed and deficient in BAL cells from asthmatic patients, and lower interferon levels were associated with greater airway hyperresponsiveness and skin prick test response positivity. Expression of Toll-like receptor (TLR) 3, TLR7, TLR8, retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA-5), TIR domain-containing adapter-inducing IFN-β (TRIF), myeloid differentiation primary response gene 88 (MyD88), caspase recruitment domain adaptor inducing IFN-β (CARDIF), IL-1 receptor-associated kinase 4 (IRAK4), IκB kinase β (IKKB), IκB kinase ι (IKKI), interferon regulatory factors 3 and 7, and rhinovirus induction of expression of the virus-inducible molecules TLR3, TLR7, RIG-I, and MDA-5 were not impaired in these interferon-deficient BAL cells in asthmatic patients. Defective rhinovirus interferon induction was not observed in blood mononuclear cells. CONCLUSIONS: Rhinovirus induction of type I interferons in BAL cells is delayed and deficient and might be a marker of more severe asthma. Defective rhinovirus interferon induction in asthmatic patients was not accompanied by differences in the expression or induction of key molecules implicated in viral induction of interferons. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/22657407/Rhinovirus_16_induced_IFN_α_and_IFN_β_are_deficient_in_bronchoalveolar_lavage_cells_in_asthmatic_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(12)00617-3 DB - PRIME DP - Unbound Medicine ER -