Bacterial CpG-DNA triggers activation and maturation of human CD11c(-), CD123(+) dendritic cells

Human plasmacytoid precursor dendritic cells (ppDC) are a major source of t ype I IFN upon exposure to virus and bacteria, yet the stimulus causing the ir maturation into DCs is unknown. After PBMC activation with immunostimula tory bacterial DNA sequences (CpG-DNA) we found that ppDC are the primary s ource of IFN-a. In fact, either CpG-DNA or dsRNA (poly(1:C) induced IFN-a f rom purified ppDC. Surprisingly, only CpG-DNA triggered purified ppDC survi val, maturation, and production of TNF, GM-CSF, IL-6, and IL-8, but not IL- 10 or IL-12. Known DC activators such as CD40 ligation triggered ppDC matur ation, but only, IL-8 production, while bacterial LPS was negative for all activation criteria. An additional finding was that only CpG-DNA could coun teract IL-4-induced apoptosis in ppDC. Therefore, CpG-DNA represents a path ogen-associated molecular pattern for ppDC. In contrast to these finding, C pG-DNA, like LPS, caused TNF, IL-6, and IL-42 release from PBMC and purifie d monocytes; however, differentiation of monocytes into DCs with GM-CSF and IL-4 unexpectedly resulted in refractoriness to CpG-DNA, but not LPS. Take n together, these results suggest that within a DC subset a multiplicity of responses can be generated by, distinct environmental stimuli and that res ponses to a given stimulus may be dissimilar between DC subsets. The Journa l of Immunology, 2001.