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House dust mite impairs antiviral response in asthma exacerbation models through its effects on TLR3

Akbarshahi, Hamid LU ; Menzel, Mandy LU ; Ramu, Sangeetha LU ; Mahmutovic Persson, Irma LU ; Bjermer, Leif LU and Uller, Lena LU (2018) In Allergy
Abstract

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 (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors (PRRs) signalling pathways and potential mechanisms of impaired interferon... (More)

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 (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors (PRRs) signalling pathways and potential mechanisms of impaired interferon response.

RESULTS: HBECs 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-lambda, TLR3, RIG-I, MDA5, IRF-3 and IRF-7. Heat-inactivation of HDM partially restored the TLR3-induced interferon response in vitro and in vivo. Our HBEC-data further showed that HDM directly affects TLR3 signalling by targeting the receptor glycosylation level.

CONCLUSIONS: Direct effects of allergens such as HDM on PRRs can present as potential mechanism for defective antiviral airway responses. Accordingly, therapeutic measures targeting inhibitory effects of allergens on antiviral PRRs may find use as a strategy to boost antiviral response and ameliorate exacerbations in asthmatic patients. This article is protected by copyright. All rights reserved.

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organization
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publication status
epub
subject
keywords
Journal Article
in
Allergy
publisher
Wiley-Blackwell
ISSN
1398-9995
DOI
10.1111/all.13378
language
English
LU publication?
yes
id
8e3848f2-812a-4a80-8c1b-30d5b9edc36d
date added to LUP
2018-01-25 11:37:15
date last changed
2018-01-25 11:37:15
@article{8e3848f2-812a-4a80-8c1b-30d5b9edc36d,
  abstract     = {<p>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.</p><p>OBJECTIVE: Our hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling.</p><p>METHODS: Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors (PRRs) signalling pathways and potential mechanisms of impaired interferon response.</p><p>RESULTS: HBECs 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-lambda, TLR3, RIG-I, MDA5, IRF-3 and IRF-7. Heat-inactivation of HDM partially restored the TLR3-induced interferon response in vitro and in vivo. Our HBEC-data further showed that HDM directly affects TLR3 signalling by targeting the receptor glycosylation level.</p><p>CONCLUSIONS: Direct effects of allergens such as HDM on PRRs can present as potential mechanism for defective antiviral airway responses. Accordingly, therapeutic measures targeting inhibitory effects of allergens on antiviral PRRs may find use as a strategy to boost antiviral response and ameliorate exacerbations in asthmatic patients. This article is protected by copyright. All rights reserved.</p>},
  author       = {Akbarshahi, Hamid and Menzel, Mandy and Ramu, Sangeetha and Mahmutovic Persson, Irma and Bjermer, Leif and Uller, Lena},
  issn         = {1398-9995},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {01},
  publisher    = {Wiley-Blackwell},
  series       = {Allergy},
  title        = {House dust mite impairs antiviral response in asthma exacerbation models through its effects on TLR3},
  url          = {http://dx.doi.org/10.1111/all.13378},
  year         = {2018},
}