Abstract
Measles virus (MV) causes profound immunosuppression, resulting in high infant mortality. The mechanisms are poorly understood, largely due to the lack of a suitable animal model. Here, we report that particular MV proteins, in the absence of MV replication, could generate a systemic immunosuppression in mice through two pathways: (1) via MV-nucleoprotein and its receptor FcgammaR on dendritic cells; and (2) via virus envelope glycoproteins and the MV-hemagglutinin cellular receptor, CD46. The effects comprise reduced hypersensitivity responses associated with impaired function of dendritic cells, decreased production of IL-12, and the loss of antigen-specific T cell proliferation. These results introduce a novel model for testing the immunosuppressive potential of anti-measles vaccines and reveal a specific mechanism of MV-induced modulation of inflammatory reactions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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Antigens, CD / genetics
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Antigens, CD / immunology*
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Division
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Dendritic Cells / immunology
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Dermatitis, Contact / immunology
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Dinitrofluorobenzene / immunology
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Disease Models, Animal
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Hemagglutinins, Viral / immunology*
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Hemocyanins / immunology
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Hypersensitivity, Delayed / chemically induced
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Hypersensitivity, Delayed / immunology
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Immunosuppressive Agents / immunology*
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Interleukin-12 / biosynthesis
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Lymph Nodes / immunology
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Measles virus / immunology*
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Membrane Cofactor Protein
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Nucleocapsid Proteins
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Nucleoproteins / immunology*
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Receptors, IgG / immunology*
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Ultraviolet Rays
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Viral Fusion Proteins / immunology*
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Viral Proteins / immunology*
Substances
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Antigens, CD
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Hemagglutinins, Viral
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Immunosuppressive Agents
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Mcp protein, mouse
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Membrane Cofactor Protein
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Membrane Glycoproteins
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Nucleocapsid Proteins
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Nucleoproteins
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Receptors, IgG
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Viral Fusion Proteins
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Viral Proteins
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hemagglutinin protein G, measles virus
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nucleoprotein, Measles virus
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Interleukin-12
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Hemocyanins
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Dinitrofluorobenzene
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keyhole-limpet hemocyanin