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Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes

Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory sy...

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Autores principales: Goritzka, Michelle, Makris, Spyridon, Kausar, Fahima, Durant, Lydia R., Pereira, Catherine, Kumagai, Yutaro, Culley, Fiona J., Mack, Matthias, Akira, Shizuo, Johansson, Cecilia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419339/
https://www.ncbi.nlm.nih.gov/pubmed/25897172
http://dx.doi.org/10.1084/jem.20140825
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author Goritzka, Michelle
Makris, Spyridon
Kausar, Fahima
Durant, Lydia R.
Pereira, Catherine
Kumagai, Yutaro
Culley, Fiona J.
Mack, Matthias
Akira, Shizuo
Johansson, Cecilia
author_facet Goritzka, Michelle
Makris, Spyridon
Kausar, Fahima
Durant, Lydia R.
Pereira, Catherine
Kumagai, Yutaro
Culley, Fiona J.
Mack, Matthias
Akira, Shizuo
Johansson, Cecilia
author_sort Goritzka, Michelle
collection PubMed
description Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory syncytial virus (RSV). Which cells produce type I IFNs upon RSV infection and how this directs immune responses to the virus, and potentially results in pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) are the major source of type I IFNs upon RSV infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)–coupled retinoic acid–inducible gene 1 (RIG-I)–like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV. This is largely attributable to loss of type I IFN–dependent induction of monocyte chemoattractants and subsequent reduced recruitment of inflammatory monocytes (infMo) to the lungs. Notably, the latter have potent antiviral activity and are essential to control infection and lessen disease severity. Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN–mediated antiviral activity. Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation.
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spelling pubmed-44193392015-11-04 Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes Goritzka, Michelle Makris, Spyridon Kausar, Fahima Durant, Lydia R. Pereira, Catherine Kumagai, Yutaro Culley, Fiona J. Mack, Matthias Akira, Shizuo Johansson, Cecilia J Exp Med Article Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory syncytial virus (RSV). Which cells produce type I IFNs upon RSV infection and how this directs immune responses to the virus, and potentially results in pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) are the major source of type I IFNs upon RSV infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)–coupled retinoic acid–inducible gene 1 (RIG-I)–like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV. This is largely attributable to loss of type I IFN–dependent induction of monocyte chemoattractants and subsequent reduced recruitment of inflammatory monocytes (infMo) to the lungs. Notably, the latter have potent antiviral activity and are essential to control infection and lessen disease severity. Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN–mediated antiviral activity. Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation. The Rockefeller University Press 2015-05-04 /pmc/articles/PMC4419339/ /pubmed/25897172 http://dx.doi.org/10.1084/jem.20140825 Text en © 2015 Goritzka et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Goritzka, Michelle
Makris, Spyridon
Kausar, Fahima
Durant, Lydia R.
Pereira, Catherine
Kumagai, Yutaro
Culley, Fiona J.
Mack, Matthias
Akira, Shizuo
Johansson, Cecilia
Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes
title Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes
title_full Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes
title_fullStr Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes
title_full_unstemmed Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes
title_short Alveolar macrophage–derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes
title_sort alveolar macrophage–derived type i interferons orchestrate innate immunity to rsv through recruitment of antiviral monocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419339/
https://www.ncbi.nlm.nih.gov/pubmed/25897172
http://dx.doi.org/10.1084/jem.20140825
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