House dust mite sensitization and exposure affects bronchial epithelial anti-microbial response to viral stimuli in patients with asthma
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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; Sverrild, Asger; Ramu, Sangeetha; Nieto-Fontarigo, Juan José; Akbarshahi, Hamid; Menzel, Mandy; Andersson, Cecilia; Tillgren, Sofia; Hvidtfeldt, Morten; Porsbjerg, Celeste; Uller, Lena.
In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 77, No. 8, 2022, p. 2498-2508.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - House dust mite sensitization and exposure affects bronchial epithelial anti-microbial response to viral stimuli in patients with asthma
AU - Cerps, Samuel
AU - Sverrild, Asger
AU - Ramu, Sangeetha
AU - Nieto-Fontarigo, Juan José
AU - Akbarshahi, Hamid
AU - Menzel, Mandy
AU - Andersson, Cecilia
AU - Tillgren, Sofia
AU - Hvidtfeldt, Morten
AU - Porsbjerg, Celeste
AU - Uller, Lena
N1 - Publisher Copyright: © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - allergy
KW - asthma
KW - bronchial epithelium
KW - exacerbation
U2 - 10.1111/all.15243
DO - 10.1111/all.15243
M3 - Journal article
C2 - 35114024
AN - SCOPUS:85124553244
VL - 77
SP - 2498
EP - 2508
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
SN - 0105-4538
IS - 8
ER -
ID: 313650406