Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+ dendritic cells.
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.
Bauer
M
M
Institute for Medical Microbiology, Immunology and Hygiene, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
Redecke
V
V
Ellwart
J W
JW
Scherer
B
B
Kremer
J P
JP
Wagner
H
H
Lipford
G B
GB
D016475:3T3 Cells; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D007370:Interferon Type I / Q000096:biosynthesis; D053650:Interleukin-3 Receptor alpha Subunit; D007519:Isoantigens / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011070:Poly I-C / Q000494:pharmacology; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D004269:DNA, Bacterial; C115022:IL3RA protein, human; D016167:Integrin alphaXbeta2; D007370:Interferon Type I; D053650:Interleukin-3 Receptor alpha Subunit; D007519:Isoantigens; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D016185:Receptors, Interleukin-3; D011070:Poly I-C