Human cytomegalovirus differentially controls B cell and T cell responses through effects on plasmacytoid dendritic cells.
Plasmacytoid dendritic cells (PDCs), the main producers of type I IFN in response to viral infection, are essential in antiviral immunity. In this study, we assessed the effect of human CMV (HCMV) infection on PDC function and on downstream B and T cell responses in vitro. HCMV infection of human PDCs was nonpermissive, as immediate-early but not late viral Ags were detected. HCMV led to partial maturation of PDCs and up-regulated MHC class II and CD83 molecules but not the costimulatory molecules CD80 and CD86. Regardless of viral replication, PDCs secreted cytokines after contact with HCMV, including IFN-alpha secretion that was blocked by inhibitory CpG, suggesting an engagement of the TLR7 and/or TLR9 pathways. In the presence of B cell receptor stimulation, soluble factors produced by HCMV-matured PDCs triggered B cell activation and proliferation. Through PDC stimulation, HCMV prompted B cell activation, but only induced Ab production in the presence of T cells or T cell secreted IL-2. Conversely, HCMV hampered the allostimulatory ability of PDCs, leading to decreased proliferation of CD4(+) and CD8(+) T cells. These findings reveal a novel mechanism by which HCMV differentially controls humoral and cell-mediate immune responses through effects on PDCs.
Varani
Stefania
S
Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Cederarv
Madeleine
M
Feld
Sari
S
Tammik
Charlotte
C
Frascaroli
Giada
G
Landini
Maria P
MP
Söderberg-Nauclér
Cecilia
C
D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology
D000906:Antibodies; D018925:Chemokines; D016207:Cytokines; D016898:Interferon-alpha; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9