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Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages.pdf (1.95 MB)

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

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posted on 2017-12-18, 14:56 authored by 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
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.

Funding

G.F. received financial support from the NC3Rs (NC/L00058X/1), and W.W.S. received financial support from the Deutsche Forschungsgemeinschaft (DFG) through EXC294 (BIOSS Centre for Biological Signalling Studies). I.C. was supported by an Alexander von Humboldt fellowship. U.F.G., M.S., and N.S. were supported by the Swiss National Science Foundation (310030B_160316) and the European Commission Initial Training Network (FP7; ADVance no. 290002). M.A.F. and M.H. were supported in part by a grant from the Leonardis foundation.

History

Citation

MBio, 2017, 8:e00670-17.

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

  • VoR (Version of Record)

Published in

MBio

Publisher

American Society for Microbiology

eissn

2150-7511

Acceptance date

2017-05-31

Copyright date

2017

Available date

2017-12-18

Publisher version

http://mbio.asm.org/content/8/4/e00670-17.abstract

Language

en

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