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IL-33 induces an antiviral signature in mast cells but enhances their permissiveness for human rhinovirus infection

IL-33 induces an antiviral signature in mast cells but enhances their permissiveness for human rhinovirus infection
IL-33 induces an antiviral signature in mast cells but enhances their permissiveness for human rhinovirus infection
Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations.
IL-33, infections, mast cells, rhinovirus
Akoto, Charlene Akua Dufie
1cd21eed-0716-468d-afa8-1c5649a70af3
Willis, Anna
ee467c30-96ad-41a2-b43f-4ba1d03ce646
Banas, Chiara Francesca
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Bell, Joseph A.
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Bryant, Dean
10ed83e8-8080-4d9c-bba5-df9d4eec3a10
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Akoto, Charlene Akua Dufie
1cd21eed-0716-468d-afa8-1c5649a70af3
Willis, Anna
ee467c30-96ad-41a2-b43f-4ba1d03ce646
Banas, Chiara Francesca
e79c0490-b1f0-4389-bdf8-ff2fe57c171e
Bell, Joseph A.
68ba55a7-95b8-4a5a-a9f2-f90afea18b11
Bryant, Dean
10ed83e8-8080-4d9c-bba5-df9d4eec3a10
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f

Akoto, Charlene Akua Dufie, Willis, Anna, Banas, Chiara Francesca, Bell, Joseph A., Bryant, Dean, Blume, Cornelia, Davies, Donna E. and Swindle, Emily J. (2022) IL-33 induces an antiviral signature in mast cells but enhances their permissiveness for human rhinovirus infection. Viruses, 14 (11). (doi:10.3390/v14112430).

Record type: Article

Abstract

Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations.

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Akoto et al 2022_PURE - Accepted Manuscript
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viruses-14-02430-v2 - Version of Record
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More information

In preparation date: 6 September 2022
Accepted/In Press date: 27 October 2022
e-pub ahead of print date: 1 November 2022
Keywords: IL-33, infections, mast cells, rhinovirus

Identifiers

Local EPrints ID: 472001
URI: http://eprints.soton.ac.uk/id/eprint/472001
PURE UUID: 312393a3-d6c7-4bc9-b0d4-d242e95d9a7a
ORCID for Dean Bryant: ORCID iD orcid.org/0000-0003-3163-608X
ORCID for Cornelia Blume: ORCID iD orcid.org/0000-0001-6133-7318
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: 23 Nov 2022 17:53
Last modified: 26 Nov 2022 02:47

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Contributors

Author: Charlene Akua Dufie Akoto
Author: Anna Willis
Author: Chiara Francesca Banas
Author: Joseph A. Bell
Author: Dean Bryant ORCID iD
Author: Cornelia Blume ORCID iD
Author: Donna E. Davies ORCID iD

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