Interferon-alpha and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets.
Dendritic cells (DCs) play a crucial role in the immune responses against infections by sensing microbial invasion through toll-like receptors (TLRs). In humans, two distinct DC subsets, CD11c(-) plasmacytoid DCs (PDCs) and CD11c(+) myeloid DCs (MDCs), have been identified and can respond to different TLR ligands, depending on the differential expression of cognate TLRs. In this study, we have examined the effect of TLR-7 ligands on human DC subsets. Both subsets expressed TLR-7 and could respond to TLR-7 ligands, which enhanced the survival of the subsets and upregulated the surface expression of costimulatory molecules such as CD40, CD80, and CD86. However, the cytokine induction pattern was distinct in that PDCs and MDCs produced interferon (IFN)-alpha and interleukin (IL)-12, respectively. In response to TLR-7 ligands, the Th1 cell supporting ability of both DC subsets was enhanced, depending on the cytokines the respective subsets produced. This study demonstrates that TLR-7 exerts its biological effect in a DC subset-specific manner.
Ito
Tomoki
T
First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan.
Amakawa
Ryuichi
R
Kaisho
Tsuneyasu
T
Hemmi
Hiroaki
H
Tajima
Kenichirou
K
Uehira
Kazutaka
K
Ozaki
Yoshio
Y
Tomizawa
Hideyuki
H
Akira
Shizuo
S
Fukuhara
Shirou
S
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D029721:Drosophila Proteins; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000378:metabolism*; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000166:cytology; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D016898:Interferon-alpha; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D018664:Interleukin-12