Targeting the function of mature dendritic cells by human cytomegalovirus: a multilayered viral defense strategy.
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.
Raftery
M J
MJ
Institute of Virology, Charité Medical School, Humboldt University Berlin, 10117 Berlin, Germany.
Schwab
M
M
Eibert
S M
SM
Samstag
Y
Y
Walczak
H
H
Schönrich
G
G
D017951:Antigen Presentation; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D053222:Fas Ligand Protein; D015967:Gene Expression Regulation, Viral; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000821:virology*; D016753:Interleukin-10 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000821:virology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D019014:fas Receptor / Q000235:genetics / Q000276:immunology
D051017:Apoptosis Regulatory Proteins; D017077:Culture Media, Conditioned; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006681:HLA-D Antigens; D007141:Immunoglobulin Fc Fragments; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D016753:Interleukin-10