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* Institute of Medical Microbiology and Hygiene and
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-
, 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-
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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