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Bauer, M.* ; Redecke, V.* ; Ellwart, J.W. ; Scherer, B.* ; Kremer, J.-P. ; Wagner, H.* ; Lipford, G.B.*

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

J. Immunol. 166, 5000-5007 (2001)
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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-alpha. In fact, either CpG-DNA or dsRNA (poly(I:C)) induced IFN-alpha 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter ANTIGEN-PRESENTING CELLS; COLONY-STIMULATING FACTOR; HUMAN BLOOD; IN-VIVO; T-CELLS; B-CELLS; IMMUNOSTIMULATORY DNA; INTERFERON-PRODUCTION; MANNOSE RECEPTOR; DOWN-REGULATION
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Zeitschrift Journal of Immunology
Quellenangaben Band: 166, Heft: 8, Seiten: 5000-5007 Artikelnummer: , Supplement: ,
Verlag American Association of Immunologists
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed