Functional characterization of ex vivo blood myeloid and plasmacytoid dendritic cells after infection with dengue virus.
Myeloid and plasmacytoid dendritic cells (mDC and pDC) are naturally distinctive subsets. We exposed both subsets to dengue virus (DV) in vitro and investigated their functional characteristics. High levels of DV replication in mDC were found to correlate with DC-SIGN expression. Production of inflammatory cytokines by mDC increased gradually after DV-infection, which was dependent on DV replication. Co-stimulatory markers were upregulated on mDC upon DV-infection. On the contrary, lower levels of DV-replication were observed in pDC, but the cytokine production in pDC was quicker and stronger. This cytokine response was not dependent on viral replication, but dependent on cell endosomal activity and TLR7, and could be also induced by purified DV genome RNA. These results clearly suggested functional differences between mDC and pDC in response to DV infection. Additionally, the TLR7-mediated recognition of DV RNA may be involved in pDC functional activation.
Sun
Peifang
P
Naval Medical Research Center, Silver Spring, MD 20910, USA. sunp@nmrc.navy.mil
Fernandez
Stefan
S
Marovich
Mary A
MA
Palmer
Dupeh R
DR
Celluzzi
Christina M
CM
Boonnak
Kobporn
K
Liang
Zhaodong
Z
Subramanian
Hemavathy
H
Porter
Kevin R
KR
Sun
Wellington
W
Burgess
Timothy H
TH
D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis; D012367:RNA, Viral / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D012367:RNA, Viral; D011956:Receptors, Cell Surface; D051199:Toll-Like Receptor 7; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C495348:TLR7 protein, human