Infection of dendritic cells by murine cytomegalovirus induces functional paralysis.
Cytomegalovirus (CMV), measles and HIV are the main human pathogens known to induce immunosuppression. Unlike measles and HIV, and despite the availability of a well studied animal model, little is known about the mechanisms that control CMV-induced immunosuppression. We hypothesized that dendritic cells (DCs), which are crucial in generating and maintaining immune responses, represent a target for CMV and that the transient, but profound, immunosuppression that accompanies CMV infection results from viral interference with DC functions. Here we show that DCs were permissive to murine CMV infection. In addition, DC infection prevented delivery of the signals required for T cell activation. Thus, CMV-mediated impairment of DC function may be crucial for virally induced immunosuppression and interleukin 2 is implicated as a key factor.
Andrews
D M
DM
Department of Microbiology, The University of Western Australia, QEII Medical Centre, Nedlands 6009, Western Australia.
Andoniou
C E
CE
Granucci
F
F
Ricciardi-Castagnoli
P
P
Degli-Esposti
M A
MA
D000818:Animals; D003587:Cytomegalovirus / Q000472:pathogenicity* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D004705:Endocytosis; D017930:Genes, Reporter; D007108:Immune Tolerance; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000276:immunology; D007763:Lac Operon; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014779:Virus Replication; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis
D008070:Lipopolysaccharides; D001616:beta-Galactosidase