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House dust mite sensitization and exposure affects bronchial epithelial anti-microbial response to viral stimuli in patients with asthma

Cerps, Samuel LU ; Sverrild, Asger ; Ramu, Sangeetha LU ; Nieto-Fontarigo, Juan José LU ; Akbarshahi, Hamid LU ; Menzel, Mandy LU ; Andersson, Cecilia ; Tillgren, Sofia LU orcid ; Hvidtfeldt, Morten and Porsbjerg, Celeste , et al. (2022) In Allergy: European Journal of Allergy and Clinical Immunology 77(8). p.2498-2508
Abstract

Introduction: Allergen exposure worsens viral-triggered asthma exacerbations and could predispose the host to secondary bacterial infections. We have previously demonstrated that exposure to house dust mite (HDM) reduced TLR-3-induced IFN-β in human bronchial epithelial cells (HBECs) from healthy donors. We hypothesize that HDM sensitization in different ways may be involved in both viral and bacterial resistance of HBECs in asthma. In this study, the role of HDM sensitization and effects of HDM exposure on viral stimulus-challenged HBECs from asthmatic donors have been explored with regard to expression and release of molecules involved in anti-viral and anti-bacterial responses, respectively. Methods: HBECs from HDM-sensitized (HDM+)... (More)

Introduction: Allergen exposure worsens viral-triggered asthma exacerbations and could predispose the host to secondary bacterial infections. We have previously demonstrated that exposure to house dust mite (HDM) reduced TLR-3-induced IFN-β in human bronchial epithelial cells (HBECs) from healthy donors. We hypothesize that HDM sensitization in different ways may be involved in both viral and bacterial resistance of HBECs in asthma. In this study, the role of HDM sensitization and effects of HDM exposure on viral stimulus-challenged HBECs from asthmatic donors have been explored with regard to expression and release of molecules involved in anti-viral and anti-bacterial responses, respectively. Methods: HBECs from HDM-sensitized (HDM+) and unsensitized (HDM-) patients with asthma were used. HBECs were exposed to HDM or heat inactivated (hi)-HDM (20 μg/ml) for 24 h prior to stimulation with the viral infection mimic, Poly(I:C), for 3 or 24 h. Samples were analyzed with ELISA and RT-qPCR for β-defensin-2, IFN-β, TSLP, and neutrophil-recruiting mediators: IL-8 and TNF-⍺. NFκB signaling proteins p105, p65, and IκB-⍺ were analyzed by Western blot. Results: Poly(I:C)-induced IFN-β expression was reduced in HBECs from HDM + compared to HDM- patients (p = 0.05). In vitro exposure of HBECs to HDM furthermore reduced anti-microbial responses to Poly(I:C) including β-defensin-2, IL-8, and TNF-⍺, along with reduced NFκB activity. This was observed in HBECs from asthma patients sensitized to HDM, as well as in non-sensitized patients. By contrast, Poly (I:C)-induced release of TSLP, a driver of T2 inflammation, was not reduced with exposure to HDM. Conclusion: Using HBECs challenged with viral infection mimic, Poly(I:C), we demonstrated that allergic sensitization to HDM was associated with impaired anti-viral immunity and that HDM exposure reduced anti-viral and anti-bacterial defense molecules, but not TSLP, across non-allergic as well as allergic asthma. These data suggest a role of HDM in the pathogenesis of asthma exacerbations evoked by viral infections including sequential viral-bacterial and viral-viral infections.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
allergy, asthma, bronchial epithelium, exacerbation
in
Allergy: European Journal of Allergy and Clinical Immunology
volume
77
issue
8
pages
2498 - 2508
publisher
Wiley-Blackwell
external identifiers
  • pmid:35114024
  • scopus:85124553244
ISSN
0105-4538
DOI
10.1111/all.15243
language
English
LU publication?
yes
id
13a63ccd-55f6-4a36-b477-fa7b05624052
date added to LUP
2022-04-14 12:34:49
date last changed
2024-06-20 01:53:50
@article{13a63ccd-55f6-4a36-b477-fa7b05624052,
  abstract     = {{<p>Introduction: Allergen exposure worsens viral-triggered asthma exacerbations and could predispose the host to secondary bacterial infections. We have previously demonstrated that exposure to house dust mite (HDM) reduced TLR-3-induced IFN-β in human bronchial epithelial cells (HBECs) from healthy donors. We hypothesize that HDM sensitization in different ways may be involved in both viral and bacterial resistance of HBECs in asthma. In this study, the role of HDM sensitization and effects of HDM exposure on viral stimulus-challenged HBECs from asthmatic donors have been explored with regard to expression and release of molecules involved in anti-viral and anti-bacterial responses, respectively. Methods: HBECs from HDM-sensitized (HDM+) and unsensitized (HDM-) patients with asthma were used. HBECs were exposed to HDM or heat inactivated (hi)-HDM (20 μg/ml) for 24 h prior to stimulation with the viral infection mimic, Poly(I:C), for 3 or 24 h. Samples were analyzed with ELISA and RT-qPCR for β-defensin-2, IFN-β, TSLP, and neutrophil-recruiting mediators: IL-8 and TNF-⍺. NFκB signaling proteins p105, p65, and IκB-⍺ were analyzed by Western blot. Results: Poly(I:C)-induced IFN-β expression was reduced in HBECs from HDM + compared to HDM- patients (p = 0.05). In vitro exposure of HBECs to HDM furthermore reduced anti-microbial responses to Poly(I:C) including β-defensin-2, IL-8, and TNF-⍺, along with reduced NFκB activity. This was observed in HBECs from asthma patients sensitized to HDM, as well as in non-sensitized patients. By contrast, Poly (I:C)-induced release of TSLP, a driver of T2 inflammation, was not reduced with exposure to HDM. Conclusion: Using HBECs challenged with viral infection mimic, Poly(I:C), we demonstrated that allergic sensitization to HDM was associated with impaired anti-viral immunity and that HDM exposure reduced anti-viral and anti-bacterial defense molecules, but not TSLP, across non-allergic as well as allergic asthma. These data suggest a role of HDM in the pathogenesis of asthma exacerbations evoked by viral infections including sequential viral-bacterial and viral-viral infections.</p>}},
  author       = {{Cerps, Samuel and Sverrild, Asger and Ramu, Sangeetha and Nieto-Fontarigo, Juan José and Akbarshahi, Hamid and Menzel, Mandy and Andersson, Cecilia and Tillgren, Sofia and Hvidtfeldt, Morten and Porsbjerg, Celeste and Uller, Lena}},
  issn         = {{0105-4538}},
  keywords     = {{allergy; asthma; bronchial epithelium; exacerbation}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{2498--2508}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Allergy: European Journal of Allergy and Clinical Immunology}},
  title        = {{House dust mite sensitization and exposure affects bronchial epithelial anti-microbial response to viral stimuli in patients with asthma}},
  url          = {{http://dx.doi.org/10.1111/all.15243}},
  doi          = {{10.1111/all.15243}},
  volume       = {{77}},
  year         = {{2022}},
}