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ABSTRACT: Background
Human rhinoviruses (HRVs) are a major trigger of asthma exacerbations, with the bronchial epithelium being the major site of HRV infection and replication. Mast cells (MCs) play a key role in asthma where their numbers are increased in the bronchial epithelium with increasing disease severity.Objective
In view of the emerging role of MCs in innate immunity and increased localization to the asthmatic bronchial epithelium, we investigated whether HRV infection of MCs generated innate immune responses which were protective against infection.Methods
The LAD2 MC line or primary human cord blood-derived MCs (CBMCs) were infected with HRV or UV-irradiated HRV at increasing multiplicities of infection (MOI) without or with IFN-? or IFN-?. After 24 h, innate immune responses were assessed by RT-qPCR and IFN protein release by ELISA. Viral replication was determined by RT-qPCR and virion release by TCID50 assay.Results
HRV infection of LAD2 MCs induced expression of IFN-?, IFN-? and IFN-stimulated genes. However, LAD2 MCs were permissive for HRV replication and release of infectious HRV particles. Similar findings were observed with CBMCs. Neutralization of the type I IFN receptor had minimal effects on viral shedding, suggesting that endogenous type I IFN signalling offered limited protection against HRV. However, augmentation of these responses by exogenous IFN-?, but not IFN-?, protected MCs against HRV infection.Conclusion and clinical relevance
MCs are permissive for the replication and release of HRV, which is prevented by exogenous IFN-? treatment. Taken together, these findings suggest a novel mechanism whereby MCs may contribute to HRV-induced asthma exacerbations.
SUBMITTER: Akoto C
PROVIDER: S-EPMC5396281 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Akoto C C Davies D E DE Swindle E J EJ
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20170126 3
<h4>Background</h4>Human rhinoviruses (HRVs) are a major trigger of asthma exacerbations, with the bronchial epithelium being the major site of HRV infection and replication. Mast cells (MCs) play a key role in asthma where their numbers are increased in the bronchial epithelium with increasing disease severity.<h4>Objective</h4>In view of the emerging role of MCs in innate immunity and increased localization to the asthmatic bronchial epithelium, we investigated whether HRV infection of MCs gen ...[more]