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Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations
Author(s) -
Akoto C.,
Davies D. E.,
Swindle E. J.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12879
Subject(s) - rhinovirus , immunology , innate immune system , biology , viral replication , permissive , asthma , immune system , viral shedding , interferon , virus , virology
Summary Background Human rhinoviruses ( HRV s) are a major trigger of asthma exacerbations, with the bronchial epithelium being the major site of HRV infection and replication. Mast cells ( MC s) 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 MC s in innate immunity and increased localization to the asthmatic bronchial epithelium, we investigated whether HRV infection of MC s generated innate immune responses which were protective against infection. Methods The LAD 2 MC line or primary human cord blood‐derived MC s ( CBMC s) were infected with HRV or UV ‐irradiated HRV at increasing multiplicities of infection ( MOI ) without or with IFN ‐β or IFN ‐λ. 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 TCID 50 assay. Results HRV infection of LAD 2 MC s induced expression of IFN ‐β, IFN ‐λ and IFN ‐stimulated genes. However, LAD 2 MC s were permissive for HRV replication and release of infectious HRV particles. Similar findings were observed with CBMC s. 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 ‐β, but not IFN ‐λ, protected MC s against HRV infection. Conclusion and Clinical Relevance MC s are permissive for the replication and release of HRV , which is prevented by exogenous IFN ‐β treatment. Taken together, these findings suggest a novel mechanism whereby MC s may contribute to HRV ‐induced asthma exacerbations.