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The Journal of Immunology, 2002, 168: 4854-4863.
Copyright © 2002 by The American Association of Immunologists

Immunostimulatory CpG-DNA Activates Murine Microglia1

Alexander H. Dalpke*, Martin K.-H. Schäfer{dagger}, Markus Frey*, Stefan Zimmermann*, Johannes Tebbe2,{dagger}, Eberhard Weihe{dagger} and Klaus Heeg3,*

* Institute of Medical Microbiology and Hygiene and {dagger} Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps-University, Marburg, Germany

Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-DNA) triggers innate immune cells through the pattern recognition receptor Toll-like receptor 9 (TLR-9). CpG-DNA possesses potent immunostimulatory effects on macrophages, dendritic cells, and B lymphocytes. Therefore, CpG-DNA contributes to inflammation during the course of bacterial infections. In contrast to other TLR-dependent microbial patterns, CpG-DNA is a strong inductor of IL-12. Thus, it acts as a Th1-polarizing agent that can be utilized as potent vaccine adjuvant. To assess the role of CpG-DNA in immune reactions in the CNS, we analyzed the effects of CpG-DNA on microglial cells in vitro and in vivo. Primary microglial cells as well as microglial cell lines express TLR-9 mRNA. Consequently, CpG-DNA activated microglial cells in vitro and induced TNF-{alpha}, IL-12p40, IL-12p70, and NO. Furthermore, MHC class II, B7-1, B7-2, and CD40 molecules were up-regulated. In addition, phagocytic activity of microglia was enhanced. After intracerebroventricular injection of CpG-DNA, microglial cells were activated and produced TNF-{alpha} and IL-12p40 transcripts, as shown by in situ hybridization. These results indicate that microglia is sensitive to CpG-DNA. Thus, bacterial DNA containing CpG motifs could not only play an important role during infections of the CNS, but also might trigger and sustain Th1-dominated immunopathogenic reactions.




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