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House dust mite impairs antiviral response in asthma exacerbation models through its effects on TLR 3
Author(s) -
Akbarshahi H.,
Menzel M.,
Ramu S.,
Mahmutovic Persson I.,
Bjermer L.,
Uller L.
Publication year - 2018
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13378
Subject(s) - house dust mite , immunology , rhinovirus , tlr3 , interferon , allergy , exacerbation , innate immune system , medicine , asthma , pattern recognition receptor , immune system , tlr7 , toll like receptor , allergen , virus
Background Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral‐induced asthma exacerbation, but little is known whether allergens may affect interferon responses. Objective Our hypothesis is that house dust mite ( HDM ) impairs viral stimulus‐induced antiviral signalling. Methods Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells ( HBEC s) and in mice using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors ( PRR s) signalling pathways and potential mechanisms of impaired interferon response. Results HBEC s and mice exposed to HDM prior to Poly(I:C) exhibited a reduced antiviral response compared to Poly(I:C) alone, including reduced IFN ‐β, IFN ‐λ, TLR 3, RIG ‐I, MDA 5, IRF ‐3 and IRF ‐7. Heat inactivation of HDM partially restored the TLR 3‐induced interferon response in vitro and in vivo. Our HBEC ‐data further showed that HDM directly affects TLR 3 signalling by targeting the receptor glycosylation level. Conclusions Direct effects of allergens such as HDM on PRR s can present as potential mechanism for defective antiviral airway responses. Accordingly, therapeutic measures targeting inhibitory effects of allergens on antiviral PRR s may find use as a strategy to boost antiviral response and ameliorate exacerbations in asthmatic patients.