Deficiency of the B cell-activating factor receptor results in limited CD169+ macrophage function during viral infection.

Autor:	Xu HC; Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany., Huang J; Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany., Khairnar V; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany., Duhan V; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany., Pandyra AA; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany., Grusdat M; Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany., Shinde P; Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany., McIlwain DR; Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA., Maney SK; Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany., Gommerman J; Department of Immunology, University of Toronto, Toronto, Ontario Canada., Löhning M; Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany., Ohashi PS; Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada Department of Immunology, University of Toronto, Toronto, Ontario Canada., Mak TW; Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada Department of Immunology, University of Toronto, Toronto, Ontario Canada., Pieper K; University Medical Centre Freiburg, Center of Chronic Immunodeficiency Freiburg, Freiburg, Germany., Sic H; University Medical Centre Freiburg, Center of Chronic Immunodeficiency Freiburg, Freiburg, Germany., Speletas M; Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, Larissa, Greece., Eibel H; University Medical Centre Freiburg, Center of Chronic Immunodeficiency Freiburg, Freiburg, Germany., Ware CF; Sanford Burnham Medical Research Institute, La Jolla, California, USA., Tumanov AV; Trudeau Institute, Saranac Lake, New York, USA., Kruglov AA; German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany., Nedospasov SA; German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany Lomonosov Moscow State University, Moscow, Russia., Häussinger D; Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany., Recher M; Primary Immunodeficiency Clinic, Medical Outpatient Division and Immunodeficiency Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland., Lang KS; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany., Lang PA; Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany Department of Molecular Medicine II, Düsseldorf, Germany Philipp.Lang@med.uni-duesseldorf.de.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2015 May; Vol. 89 (9), pp. 4748-59. Date of Electronic Publication: 2015 Feb 11.
DOI:	10.1128/JVI.02976-14
Abstrakt:	Unlabelled: The B cell-activating factor (BAFF) is critical for B cell development and humoral immunity in mice and humans. While the role of BAFF in B cells has been widely described, its role in innate immunity remains unknown. Using BAFF receptor (BAFFR)-deficient mice, we characterized BAFFR-related innate and adaptive immune functions following infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV). We identified a critical role for BAFFR signaling in the generation and maintenance of the CD169(+) macrophage compartment. Consequently, Baffr(-) (/) (-) mice exhibited limited induction of innate type I interferon production after viral infection. Lack of BAFFR signaling reduced virus amplification and presentation following viral infection, resulting in highly reduced antiviral adaptive immune responses. As a consequence, BAFFR-deficient mice showed exacerbated and fatal disease after viral infection. Mechanistically, transient lack of B cells in Baffr(-) (/) (-) animals resulted in limited lymphotoxin expression, which is critical for maintenance of CD169(+) cells. In conclusion, BAFFR signaling affects both innate and adaptive immune activation during viral infections. Importance: Viruses cause acute and chronic infections in humans resulting in millions of deaths every year. Innate immunity is critical for the outcome of a viral infection. Innate type I interferon production can limit viral replication, while adaptive immune priming by innate immune cells induces pathogen-specific immunity with long-term protection. Here, we show that BAFFR deficiency not only perturbed B cells, but also resulted in limited CD169(+) macrophages. These macrophages are critical in amplifying viral particles to trigger type I interferon production and initiate adaptive immune priming. Consequently, BAFFR deficiency resulted in reduced enforced viral replication, limited type I interferon production, and reduced adaptive immunity compared to BAFFR-competent controls. As a result, BAFFR-deficient mice were predisposed to fatal viral infections. Thus, BAFFR expression is critical for innate immune activation and antiviral immunity. (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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