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Immunology - Infectious Diseases - Respiratory Medicine

Transforming Growth Factor-Beta Promotes Rhinovirus Replication in Bronchial Epithelial Cells by Suppressing the Innate Immune Response
Published: Thursday, September 06, 2012
Author: Nicole Bedke et al.

by Nicole Bedke, David Sammut, Ben Green, Valia Kehagia, Patrick Dennison, Gisli Jenkins, Amanda Tatler, Peter H. Howarth, Stephen T. Holgate, Donna E. Davies

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-ß, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-ß2 increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-ß antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-ß2 levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-ß on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-ß and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-ß contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.