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 antigens 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.