Bacterial CpG-DNA Triggers Activation and Maturation of Human CD11c-, CD123+ Dendritic Cells

• Published in: The Journal of immunology (1950) 2001-04, Vol.166 (8), p.5000-5007
• Main Authors: Bauer, Marc, Redecke, Vanessa, Ellwart, Joachim W, Scherer, Barbara, Kremer, Jean-Pierre, Wagner, Hermann, Lipford, Grayson B
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adjuvants, Immunologic - pharmacology; Animals; Cell Differentiation - immunology; Cell Survival - drug effects; Cell Survival - immunology; Cells, Cultured; CpG Islands - immunology; Cytokines - biosynthesis; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - microbiology; DNA, Bacterial - pharmacology; Escherichia coli - immunology; Humans; Integrin alphaXbeta2 - biosynthesis; Interferon Type I - biosynthesis; Interleukin-3 Receptor alpha Subunit; Isoantigens - physiology; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Lipopolysaccharides - pharmacology; Mice; Monocytes - cytology; Monocytes - immunology; Oligodeoxyribonucleotides - pharmacology; Plasma Cells - cytology; Plasma Cells - immunology; Plasma Cells - metabolism; Plasma Cells - microbiology; Poly I-C - pharmacology; Receptors, Interleukin-3 - biosynthesis; Stem Cells - cytology; Stem Cells - immunology; Stem Cells - metabolism; Stem Cells - microbiology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.8.5000

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.