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J Virol. 2018 Jan 17;92(3). pii: e01637-17. doi: 10.1128/JVI.01637-17. Print 2018 Feb 1.

Tumor Necrosis Factor-Mediated Survival of CD169+ Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection.

Author information

1
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
2
Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
3
Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
4
Computational Biology of Infection Research, Helmholtz Center for Infection Research, Braunschweig, Germany.
5
Institute of Virology, TU Munich, Munich, Germany.
6
Institute of Molecular Immunology, Technische Universität Munich and Helmholtz Zentrum Munich, Munich, Germany.
7
Department of Rheumatology, Hiller Research Center Rheumatology, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
8
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
9
Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales (IPATEC), Universidad Nacional del Comahue-CONICET, Bariloche, Argentina.
10
Institute for Virology of the University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
11
Department of Cell Biology, Vrije University Medical Center, Amsterdam, Netherlands.
12
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
13
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
14
Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
15
Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
16
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität Munich, Munich, Germany.
17
German Cancer Consortium (DKTK), partner site Munich, Germany.
18
German Center for Infection Research (DZIF), partner site Munich, Germany.
19
Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, Munich, Germany.
20
Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
21
Department of Infection and Immunity, Experimental and Molecular Immunology, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
22
Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
23
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
24
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany langp@uni-duesseldorf.de.
#
Contributed equally

Abstract

Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169+ cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169+ cells during viral infections remain unclear. Here, we show that tumor necrosis factor is produced by CD11b+ Ly6C+ Ly6G+ cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169+ cells and in reduced type I interferon (IFN-I) production during VSV infection, with a severe disease outcome. Specifically, TNF triggered RelA translocation into the nuclei of CD169+ cells; this translocation was inhibited when the paracaspase MALT-1 was absent. Consequently, MALT1 deficiency resulted in reduced VSV replication, defective innate immune activation, and development of severe disease. These findings indicate that TNF mediates the maintenance of CD169+ cells and innate and adaptive immune activation during VSV infection.IMPORTANCE Over the last decade, strategically placed CD169+ metallophilic macrophages in the marginal zone of the murine spleen and lymph nodes (LN) have been shown to play a very important role in host defense against viral pathogens. CD169+ macrophages have been shown to activate innate and adaptive immunity via "enforced virus replication," a controlled amplification of virus particles. However, the factors regulating the CD169+ macrophages remain to be studied. In this paper, we show that after vesicular stomatitis virus infection, phagocytes produce tumor necrosis factor (TNF), which signals via TNFR1, and promote enforced virus replication in CD169+ macrophages. Consequently, lack of TNF or TNFR1 resulted in defective immune activation and VSV clearance.

KEYWORDS:

MALT1; NF-κB; TNF; innate immunity; interferon; interferons; tumor necrosis factor

PMID:
29142134
PMCID:
PMC5774891
DOI:
10.1128/JVI.01637-17
[Indexed for MEDLINE]
Free PMC Article

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