Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages

ABSTRACT The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO m...

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Autores principales:	Mareike D. Maler, Peter J. Nielsen, Nicole Stichling, Idan Cohen, Zsolt Ruzsics, Connor Wood, Peggy Engelhard, Maarit Suomalainen, Ildiko Gyory, Michael Huber, Joachim Müller-Quernheim, Wolfgang W. A. Schamel, Siamon Gordon, Thilo Jakob, Stefan F. Martin, Willi Jahnen-Dechent, Urs F. Greber, Marina A. Freudenberg, György Fejer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	IL-1α MARCO MPI cells adenovirus cGAS cytokines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9c98ffb98e534f1895fead53be5d0402
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spelling	oai:doaj.org-article:9c98ffb98e534f1895fead53be5d04022021-11-15T15:51:43ZKey Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages10.1128/mBio.00670-172150-7511https://doaj.org/article/9c98ffb98e534f1895fead53be5d04022017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00670-17https://doaj.org/toc/2150-7511ABSTRACT The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo. Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo. The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages. Its role in antiviral macrophage responses is largely unexplored. Here, we studied whether the differential expression of MARCO might contribute to the various susceptibilities of macrophage subtypes to adenovirus. We demonstrate that MARCO significantly enhances adenovirus infection and innate responses in macrophages. These results help to understand adenoviral pathogenesis and may open new possibilities to influence the outcome of infection with adenoviruses or adenovirus vectors.Mareike D. MalerPeter J. NielsenNicole StichlingIdan CohenZsolt RuzsicsConnor WoodPeggy EngelhardMaarit SuomalainenIldiko GyoryMichael HuberJoachim Müller-QuernheimWolfgang W. A. SchamelSiamon GordonThilo JakobStefan F. MartinWilli Jahnen-DechentUrs F. GreberMarina A. FreudenbergGyörgy FejerAmerican Society for MicrobiologyarticleIL-1αMARCOMPI cellsadenoviruscGAScytokinesMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	IL-1α MARCO MPI cells adenovirus cGAS cytokines Microbiology QR1-502
spellingShingle	IL-1α MARCO MPI cells adenovirus cGAS cytokines Microbiology QR1-502 Mareike D. Maler Peter J. Nielsen Nicole Stichling Idan Cohen Zsolt Ruzsics Connor Wood Peggy Engelhard Maarit Suomalainen Ildiko Gyory Michael Huber Joachim Müller-Quernheim Wolfgang W. A. Schamel Siamon Gordon Thilo Jakob Stefan F. Martin Willi Jahnen-Dechent Urs F. Greber Marina A. Freudenberg György Fejer Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages
description	ABSTRACT The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo. Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo. The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages. Its role in antiviral macrophage responses is largely unexplored. Here, we studied whether the differential expression of MARCO might contribute to the various susceptibilities of macrophage subtypes to adenovirus. We demonstrate that MARCO significantly enhances adenovirus infection and innate responses in macrophages. These results help to understand adenoviral pathogenesis and may open new possibilities to influence the outcome of infection with adenoviruses or adenovirus vectors.
format	article
author	Mareike D. Maler Peter J. Nielsen Nicole Stichling Idan Cohen Zsolt Ruzsics Connor Wood Peggy Engelhard Maarit Suomalainen Ildiko Gyory Michael Huber Joachim Müller-Quernheim Wolfgang W. A. Schamel Siamon Gordon Thilo Jakob Stefan F. Martin Willi Jahnen-Dechent Urs F. Greber Marina A. Freudenberg György Fejer
author_facet	Mareike D. Maler Peter J. Nielsen Nicole Stichling Idan Cohen Zsolt Ruzsics Connor Wood Peggy Engelhard Maarit Suomalainen Ildiko Gyory Michael Huber Joachim Müller-Quernheim Wolfgang W. A. Schamel Siamon Gordon Thilo Jakob Stefan F. Martin Willi Jahnen-Dechent Urs F. Greber Marina A. Freudenberg György Fejer
author_sort	Mareike D. Maler
title	Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages
title_short	Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages
title_full	Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages
title_fullStr	Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages
title_full_unstemmed	Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages
title_sort	key role of the scavenger receptor marco in mediating adenovirus infection and subsequent innate responses of macrophages
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/9c98ffb98e534f1895fead53be5d0402
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Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages

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