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Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations

Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations
Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations
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 localisation 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. Neutralisation 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
0954-7894
1-31
Akoto, Charlene
1cd21eed-0716-468d-afa8-1c5649a70af3
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Akoto, Charlene
1cd21eed-0716-468d-afa8-1c5649a70af3
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f

Akoto, Charlene, Davies, Donna E. and Swindle, Emily J. (2016) Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations. Clinical & Experimental Allergy, 1-31. (doi:10.1111/cea.12879). (PMID:28008678)

Record type: Article

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 localisation 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. Neutralisation 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

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Akoto et al_2016_for eprints.pdf - Accepted Manuscript
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More information

Submitted date: 2 September 2016
Accepted/In Press date: 22 November 2016
e-pub ahead of print date: 23 December 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 404282
URI: https://eprints.soton.ac.uk/id/eprint/404282
ISSN: 0954-7894
PURE UUID: 9183d87c-963f-4731-ad3a-a99f4cdfdf91
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Emily J. Swindle: ORCID iD orcid.org/0000-0003-3644-7747

Catalogue record

Date deposited: 05 Jan 2017 11:51
Last modified: 10 Dec 2019 06:17

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