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ABSTRACT The innate immune system limits viral replication via type I interferon and also induces the presentation of viral antigens to cells of the adaptive immune response. Using infection

of mice with vesicular stomatitis virus, we analyzed how the innate immune system inhibits viral propagation but still allows the presentation of antigen to cells of the adaptive immune

response. We found that expression of the gene encoding the inhibitory protein Usp18 in metallophilic macrophages led to lower type I interferon responsiveness, thereby allowing locally

restricted replication of virus. This was essential for the induction of adaptive antiviral immune responses and, therefore, for preventing the fatal outcome of infection. In conclusion, we

found that enforced viral replication in marginal zone macrophages was an immunological mechanism that ensured the production of sufficient antigen for effective activation of the adaptive

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DIVERSITY OF CELL DEATH SIGNALING PATHWAYS IN MACROPHAGES UPON INFECTION WITH MODIFIED VACCINIA VIRUS ANKARA (MVA) Article

Open access 28 October 2021 IKKΕ ISOFORM SWITCHING GOVERNS THE IMMUNE RESPONSE AGAINST EV71 INFECTION Article Open access 02 June 2021 LY6E IMPAIRS CORONAVIRUS FUSION AND CONFERS IMMUNE

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K. Schättel for technical support. Supported by the Alexander von Humboldt Foundation (SKA-2008 to K.S.L. and SKA-2010 to P.A.L.), Collaborative Research Center SFB575, Experimental

Hepatology (coordinator, D.H.; Deutsche Forschungsgemeinschaft grant LA1419/3-1 to K.S.L. and SFB-TR19 to K.K. and R.K.; FOR729 to K.P.; SFB/Transregio 60 (coordinator, M. Roggendorf), the

MOI Manchot Graduate School (Jürgen Manchot Foundation), the Swiss National Science Foundation (PASMP3-127678/1 to M.R.) and the US National Institutes of Health (R01 HL091549 for

_Usp18_-related work in the D.-E.Z. laboratory). AUTHOR INFORMATION Author notes * Mike Recher, Philipp A Lang and Karl S Lang: These authors contributed equally to this manuscript. AUTHORS

AND AFFILIATIONS * Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Düsseldorf, Germany Nadine Honke, Namir Shaabani, Nicole Gailus, Melanie

Grusdat, Dieter Häussinger, Philipp A Lang & Karl S Lang * Institute for Pathology, Heinrich-Heine-University, Düsseldorf, Germany Giuseppe Cadeddu & Stephan E Baldus * Institute of

Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, Düsseldorf, Germany Ursula R Sorg & Klaus Pfeffer * Department of Pathology, Division of Biological Sciences and

Moores University of California San Diego Cancer Center, University of California San Diego, La Jolla, California, USA Dong-Er Zhang & Christoph Burkart * Institute for Virology,

Heinrich-Heine-University, Düsseldorf, Germany Mirko Trilling & Hartmut Hengel * Department of Molecular Pathology, Eberhard Karls University Tübingen, Tübingen, Germany Karin Klingel, 

Martina Sauter & Reinhard Kandolf * Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands Nico van Rooijen * Department of

Rheumatology and Clinical Immunology, Charité-University Medicine Berlin and German Rheumatism Research Center, Berlin, Germany Max Löhning * Laboratory for Innate Cellular Immunity, RIKEN

Research Center for Allergy and Immunology, Yokohama, Japan Masato Tanaka * Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA Mike Recher *

Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada Philipp A Lang * Institute for Immunology, University of

Essen, Essen, Germany Karl S Lang Authors * Nadine Honke View author publications You can also search for this author inPubMed Google Scholar * Namir Shaabani View author publications You

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author inPubMed Google Scholar CONTRIBUTIONS N.H. planned and did most experiments; N.S. planned and did several experiments; G.C. and S.E.B. did laser-capture dissection; U.R.S. contributed

to _Ltbr_−/− mouse experiments; D.-E.Z. contributed to experiments on _Usp18_; M.T. and C.B. contributed to transfection experiments; K.K., M.S. and R.K. did and interpreted _in situ_

hybridization; N.G. did _in vitro_ experiments; N.v.R. contributed to macrophage depletion experiments; M.G. did _in vitro_ stimulation of DCs; M.L., H.H., K.P., M.T., D.H. and M.R.

discussed and interpreted data and helped to write the manuscript; and P.A.L. and K.S.L. initiated and designed the study and wrote most of the manuscript. CORRESPONDING AUTHORS

Correspondence to Philipp A Lang or Karl S Lang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT

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viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. _Nat Immunol_ 13, 51–57 (2012). https://doi.org/10.1038/ni.2169 Download citation *

Received: 03 August 2011 * Accepted: 19 October 2011 * Published: 20 November 2011 * Issue Date: January 2012 * DOI: https://doi.org/10.1038/ni.2169 SHARE THIS ARTICLE Anyone you share the

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