Human cytomegalovirus differentially controls B cell and T cell responses through effects on plasmacytoid dendritic cells |
| |
Authors: | Varani Stefania Cederarv Madeleine Feld Sari Tammik Charlotte Frascaroli Giada Landini Maria P Söderberg-Nauclér Cecilia |
| |
Affiliation: | Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|