2001
DOI: 10.4049/jimmunol.166.8.5000
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Bacterial CpG-DNA Triggers Activation and Maturation of Human CD11c−, CD123+ Dendritic Cells

Abstract: Human plasmacytoid precursor dendritic cells (ppDC) are a major source of type I IFN upon exposure to virus and bacteria, yet the stimulus causing their maturation into DCs is unknown. After PBMC activation with immunostimulatory bacterial DNA sequences (CpG-DNA) we found that ppDC are the primary source of IFN-α. In fact, either CpG-DNA or dsRNA (poly(I:C)) induced IFN-α from purified ppDC. Surprisingly, only CpG-DNA triggered purified ppDC survival, maturation, and production of TNF, GM-CSF, IL-6, and IL-8, … Show more

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Cited by 268 publications
(196 citation statements)
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“…Two potential cell populations are plasmacytoid precursor dendritic cells (p-preDC) and FC. Reports have documented the ability of p-preDC to induce the differentiation of naïve CD4 + CD25 − T cells into FoxP3 + CD4 + CD25 + regulatory T cells in vitro [10][11][12][13][14][15][16][17]. Similarly, we have reported that FC can also induce the in vitro development of FoxP3 + CD4 + CD25 + regulatory T cells [5].…”
Section: Introductionsupporting
confidence: 64%
See 1 more Smart Citation
“…Two potential cell populations are plasmacytoid precursor dendritic cells (p-preDC) and FC. Reports have documented the ability of p-preDC to induce the differentiation of naïve CD4 + CD25 − T cells into FoxP3 + CD4 + CD25 + regulatory T cells in vitro [10][11][12][13][14][15][16][17]. Similarly, we have reported that FC can also induce the in vitro development of FoxP3 + CD4 + CD25 + regulatory T cells [5].…”
Section: Introductionsupporting
confidence: 64%
“…Studies have well documented that expression of inflammatory cytokines IL6, TNFα, and IL12 can be induced following CpG-stimulation of TLR9 on p-preDC [10][11][12][13][14][15][16][17]. The expression and function of these cytokines has been linked to the activation and maturation of p-preDC [22,[24][25][26], and therefore are important in the establishment of regulatory T cell networks.…”
Section: Cpg-stimulated Fc-cd3ε − Cells Express Higher Levels Of Inflmentioning
confidence: 99%
“…In mouse PDC, TAK-1/MAP3K7 activates the mitogen-activated protein kinase (MAPK) pathway that upregulates costimulatory molecule expression (e.g., CD40, CD80 or CD86) 36 . Both human and mouse PDC have been shown to secrete TNF-α 46, 45, 46 , IL-6 46, 45, 46 , IL-8 4547 or granulocyte macrophage colony-stimulating factor (GM-CSF) 45 . This TLR-induced cytokine synthesis is regulated in PDC by the translocation of NF-κB, p38 MAPK and c-Jun N-terminal kinase (JNK) into the nucleus.…”
Section: The Innate Immune Functions Of Plasmacytoid Dendritic Cellsmentioning
confidence: 99%
“…TLR3 is involved in recognition and signal transduction induced by double-stranded (ds) RNA synthesized from viruses [26]. In accordance with the TLR expression, IPCs recognize CpG-oligonucleotides (ODNs), but not PGN or LPS, and thereby rapidly produce IFN-␣/␤ and develop into mature DCs [14,[27][28][29]. By contrast, blood CD11c ϩ mDCs and monocytes respond to PGN or LPS, but not CpG-ODNs, to produce different sets of proinflammatory cytokines (i.e.…”
Section: Differential Responsiveness Through Tlrmentioning
confidence: 99%
“…In fact, every susceptible TLR ligand can induce IL-12 production from immature mDCs and monocytes [16]. Also, when IPCs respond to ligands for TLR7 [18] or TLR9 [29], IPC-derived DCs can induce IFN-␥ producing Th cells through IFN-␣/␤ suggesting that IPCs acquire Th1 (or Th1-like) inducing activity upon microbial invasion. In addition, the production of IL-12 by myeloid DCs triggered by some microbial stimuli [52,53] and the production of IFN-␣ by IPCs stimulated by CpG-ODN [15] is amplified by CD40 ligation.…”
Section: Ipc-derived Dcs In Adaptive Immunity Possible Involvement Imentioning
confidence: 99%