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Epithelial derived TGF-β1 acts as a pro-viral factor in the lung during influenza A infection

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Title: Epithelial derived TGF-β1 acts as a pro-viral factor in the lung during influenza A infection
Authors: Denney, L
Branchett, W
Gregory, L
Oliver, R
Lloyd, CM
Item Type: Journal Article
Abstract: Mucosal surfaces are under constant bombardment from potentially antigenic particles and so must maintain a balance between homeostasis and inappropriate immune activation and consequent pathology. Epithelial cells have a vital role orchestrating pulmonary homeostasis and defense against pathogens. TGF-β regulates an array of immune responses—both inflammatory and regulatory—however, its function is highly location- and context-dependent. We demonstrate that epithelial-derived TGF-β acts as a pro-viral factor suppressing early immune responses during influenza A infection. Mice specifically lacking bronchial epithelial TGF-β1 (epTGFβKO) displayed marked protection from influenza-induced weight loss, airway inflammation, and pathology. However, protection from influenza-induced pathology was not associated with a heightened lymphocytic immune response. In contrast, the kinetics of interferon beta (IFNβ) release into the airways was significantly enhanced in epTGFβKO mice compared with control mice, with elevated IFNβ on day 1 in epTGFβKO compared with control mice. This induced a heighted antiviral state resulting in impaired viral replication in epTGFβKO mice. Thus, epithelial-derived TGF-β acts to suppress early IFNβ responses leading to increased viral burden and pathology. This study demonstrates the importance of the local epithelial microenvironmental niche in shaping initial immune responses to viral infection and controlling host disease.
Issue Date: 25-Oct-2017
Date of Acceptance: 26-Jul-2017
URI: http://hdl.handle.net/10044/1/50255
DOI: https://dx.doi.org/10.1038/mi.2017.77
ISSN: 1933-0219
Publisher: Nature Publishing Group
Start Page: 523
End Page: 535
Journal / Book Title: Mucosal Immunology
Volume: 11
Copyright Statement: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution4.0 InternationalLicense.Theimagesor other thirdpartymaterialinthisarticleareincludedinthearticle’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Wellcome Trust
Medical Research Council (MRC)
Medical Research Council (MRC)
Wellcome Trust
Funder's Grant Number: 087618/Z/08/Z
Keywords: 06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:National Heart and Lung Institute