HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deng, G.-M. Articles by Tarkowski, A. Search for Related Content PubMed PubMed Citation Articles by Deng, G.-M. Articles by Tarkowski, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Meningitis Hazardous Substances DB NITRIC OXIDE

Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis¹

Department of Rheumatology, Göteborg University, Göteborg, Sweden

Unmethylated CpG motifs are frequently found in bacterial DNA, and have recently been shown to exert immunostimulatory effects on leukocytes. Since bacterial infections in the CNS will lead to local release of prokaryotic DNA, we wanted to investigate whether such an event might trigger meningitis. To that end, we have intracisternally injected mice and rats with bacterial DNA and oligonucleotides containing CpG motifs. Histopathological signs of meningitis were evident within 12 h and lasted for at least 14 days, and were characterized by an influx of monocytic, Mac-3⁺ cells and by a lack of T lymphocytes. To study the mechanisms whereby unmethylated CpG DNA gives rise to meningitis, we deleted the monocyte/macrophage population leading to abrogation of brain inflammation. Also, interaction with NF-B using antisense technology led to down-regulation of proinflammatory cytokine production and frequency of meningitis. Furthermore, specific interactions with vascular selectin expression and inhibition of NO synthase led to a significant amelioration of meningitis, altogether indicating that this condition is dependent on macrophages and their products. In contrast, neutrophils, NK cells, T/B lymphocytes, IL-12, and complement system were not instrumental in meningitis triggered by bacterial DNA containing CpG motifs. This study proves that bacterial DNA containing unmethylated CpG motifs induces meningitis, and indicates that this condition is mediated in vivo by activated macrophages.

This article has been cited by other articles:

				P. Knuefermann, M. Schwederski, M. Velten, P. Krings, H. Ehrentraut, M. Rudiger, O. Boehm, K. Fink, U. Dreiner, C. Grohe, et al. Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9 Cardiovasc Res, April 1, 2008; 78(1): 26 - 35. [Abstract] [Full Text] [PDF]

				R. Zhou, H. Wei, R. Sun, J. Zhang, and Z. Tian NKG2D recognition mediates Toll-like receptor 3 signaling-induced breakdown of epithelial homeostasis in the small intestines of mice PNAS, May 1, 2007; 104(18): 7512 - 7515. [Abstract] [Full Text] [PDF]

				H.-J. Anders, B. Banas, and D. Schlondorff Signaling Danger: Toll-Like Receptors and their Potential Roles in Kidney Disease J. Am. Soc. Nephrol., April 1, 2004; 15(4): 854 - 867. [Abstract] [Full Text] [PDF]

				H.-J. Anders, B. Banas, Y. Linde, L. Weller, C. D. Cohen, M. Kretzler, S. Martin, V. Vielhauer, D. Schlondorff, and H.-J. Grone Bacterial CpG-DNA Aggravates Immune Complex Glomerulonephritis: Role of TLR9-Mediated Expression of Chemokines and Chemokine Receptors J. Am. Soc. Nephrol., February 1, 2003; 14(2): 317 - 326. [Abstract] [Full Text] [PDF]