Abstract
Human cytomegalovirus (HCMV) can suppress and evade the immune system. We have identified as a mechanism the ability of HCMV to infect dendritic cells (DC), which initiate the antiviral immune response. HCMV-infected DC show enhanced expression of costimulatory molecules. In contrast, MHC molecules are partially downregulated, leading to a reduced antigen-presenting capacity. Moreover, the apoptosis-inducing ligands CD95L (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are upregulated, thereby enabling HCMV-infected DC to delete activated T lymphocytes. This additional layer of viral defense is complemented by nondeletional mechanisms, which suppress surviving T cells. Thus, infection of DC allows the virus to blunt the antiviral T cell response by a multilayered defense strategy and could play a pivotal role in HCMV-triggered immunosuppression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigen Presentation*
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Apoptosis
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Apoptosis Regulatory Proteins
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Culture Media, Conditioned / pharmacology
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Cytomegalovirus / physiology*
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Cytomegalovirus Infections / immunology*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / virology*
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Fas Ligand Protein
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Gene Expression Regulation, Viral
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HLA-D Antigens / biosynthesis
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HLA-D Antigens / genetics
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Humans
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Immunoglobulin Fc Fragments / genetics
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Immunoglobulin Fc Fragments / immunology
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Immunologic Deficiency Syndromes / virology*
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Interleukin-10 / pharmacology
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Killer Cells, Natural / virology
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Lymphocyte Activation
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / physiology
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Recombinant Fusion Proteins / immunology
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T-Lymphocyte Subsets / immunology
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
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fas Receptor / genetics
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fas Receptor / immunology
Substances
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Apoptosis Regulatory Proteins
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Culture Media, Conditioned
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FASLG protein, human
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Fas Ligand Protein
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HLA-D Antigens
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Immunoglobulin Fc Fragments
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Membrane Glycoproteins
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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Recombinant Fusion Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFRSF10B protein, human
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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fas Receptor
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Interleukin-10