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*
Institute for Medical Microbiology, Immunology and Hygiene, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; and
Institute for Experimental Hematology, GSF National Research Center for Environment and Health, Munich, Germany
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-
. In
fact, either CpG-DNA or dsRNA (poly(I:C)) induced IFN- from purified
ppDC. Surprisingly, only CpG-DNA triggered purified ppDC survival,
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 maturation, but only IL-8 production, while bacterial LPS was
negative for all activation criteria. An additional finding was that
only CpG-DNA could counteract IL-4-induced apoptosis in ppDC.
Therefore, CpG-DNA represents a pathogen-associated molecular pattern
for ppDC. In contrast to these finding, CpG-DNA, like LPS, caused TNF,
IL-6, and IL-12 release from PBMC and purified monocytes; however,
differentiation of monocytes into DCs with GM-CSF and IL-4 unexpectedly
resulted in refractoriness to CpG-DNA, but not LPS. Taken together,
these results suggest that within a DC subset a multiplicity of
responses can be generated by distinct environmental stimuli and that
responses to a given stimulus may be dissimilar between DC
subsets.
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