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Alveolar Macrophages Can Control Respiratory Syncytial Virus Infection in the Absence of Type I Interferons

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Title: Alveolar Macrophages Can Control Respiratory Syncytial Virus Infection in the Absence of Type I Interferons
Authors: Makris, S
Bajorek, M
Culley, F
Goritzka, M
Johansson, C
Item Type: Journal Article
Abstract: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections. Immunity to RSV is initiated upon detection of the virus by pattern recognition receptors, such as RIG-I-like receptors. RIG-I-like receptors signal via MAVS to induce the synthesis of proinflammatory mediators, including type I interferons (IFNs), which trigger and shape antiviral responses and protect cells from infection. Alveolar macrophages (AMs) are amongst the first cells to encounter invading viruses and the ones producing type I IFNs. However, it is unclear whether IFNs act to prevent AMs from serving as vehicles for viral replication. In this study, primary AMs from MAVS (Mavs-/-)- or type I IFN receptor (Ifnar1-/-)-deficient mice were exposed to RSV ex vivo. Wild-type (wt) AMs but not Mavs-/- and Ifnar1-/- AMs produced inflammatory mediators in response to RSV. Furthermore, Mavs-/- and Ifnar1-/- AMs accumulated more RSV proteins than wt AMs, but the infection was abortive. Thus, RIG-I-like receptor-MAVS and IFNAR signalling are important for the induction of proinflammatory mediators from AMs upon RSV infection, but this signalling is not central for controlling viral replication. The ability to restrict viral replication makes AMs ideal sensors of RSV infection and important initiators of immune responses in the lung.
Issue Date: 16-Jul-2016
Date of Acceptance: 16-May-2016
URI: http://hdl.handle.net/10044/1/33247
DOI: http://dx.doi.org/10.1159/000446824
ISSN: 1662-8128
Publisher: Karger
Journal / Book Title: Journal of Innate Immunity
Volume: 8
Issue: 5
Copyright Statement: © 2016 The Author(s). This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY) (http://www.karger.com/Services/ OpenAccessLicense). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.
Sponsor/Funder: Medical Research Council (MRC)
Commission of the European Communities
Rosetrees Trust
National Heart and Lung Institute Foundation
Funder's Grant Number: G0800311
321931
M370
Spiros Makris
Keywords: Medical And Health Sciences
Publication Status: Published
Appears in Collections:National Heart and Lung Institute