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Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response

Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response
Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.
1932-6203
e44580
Bedke, Nicole
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Sammut, David
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Green, Ben
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Kehagia, Valia
c7d748ed-383f-48e5-bbfa-c36c9dc07068
Dennison, Patrick
45948aae-8297-4459-be11-56e85f51ae73
Jenkins, Gisli
6a449582-a746-4bce-9ccc-9aa494f3e56e
Tatler, Amanda
38454941-df00-45f9-9321-d738ad7a497c
Howarth, Peter H.
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Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Bedke, Nicole
981dbd61-1912-4231-b6d5-42520c38178d
Sammut, David
0c7ac14b-6c2e-4d45-85a0-327703d1afd0
Green, Ben
11aad629-bfdc-47a2-ba4a-343f3f7a52c5
Kehagia, Valia
c7d748ed-383f-48e5-bbfa-c36c9dc07068
Dennison, Patrick
45948aae-8297-4459-be11-56e85f51ae73
Jenkins, Gisli
6a449582-a746-4bce-9ccc-9aa494f3e56e
Tatler, Amanda
38454941-df00-45f9-9321-d738ad7a497c
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Bedke, Nicole, Sammut, David, Green, Ben, Kehagia, Valia, Dennison, Patrick, Jenkins, Gisli, Tatler, Amanda, Howarth, Peter H., Holgate, Stephen T. and Davies, Donna E. (2012) Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response. PLoS ONE, 7 (9), e44580. (doi:10.1371/journal.pone.0044580). (PMID:22970254)

Record type: Article

Abstract

Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.

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Published date: 6 September 2012
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 346650
URI: https://eprints.soton.ac.uk/id/eprint/346650
ISSN: 1932-6203
PURE UUID: dce46337-e0d8-4f3e-a5c3-f83a21b2a023
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 16 Jan 2013 12:06
Last modified: 05 Nov 2019 02:09

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Contributors

Author: Nicole Bedke
Author: David Sammut
Author: Ben Green
Author: Valia Kehagia
Author: Patrick Dennison
Author: Gisli Jenkins
Author: Amanda Tatler
Author: Donna E. Davies ORCID iD

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