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Infection and Immunity, February 2003, p. 850-856, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.850-856.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

DNA from Periodontopathogenic Bacteria Is Immunostimulatory for Mouse and Human Immune Cells

Claudia Nonnenmacher,1,2 Alexander Dalpke,1 Stefan Zimmermann,1 Lavin Flores-de-Jacoby,2 Reinier Mutters,1 and Klaus Heeg1*

Institute of Medical Microbiology and Hygiene,1 Department of Periodontology, Philipps University, Marburg, Germany2

Received 19 June 2002/ Returned for modification 4 September 2002/ Accepted 8 November 2002

Although bacterial DNA (bDNA) containing unmethylated CpG motifs stimulates innate immune cells through Toll-like receptor 9 (TLR-9), its precise role in the pathophysiology of diseases is still equivocal. Here we examined the immunostimulatory effects of DNA extracted from periodontopathogenic bacteria. A major role in the etiology of periodontal diseases has been attributed to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Peptostreptococcus micros. We therefore isolated DNA from these bacteria and stimulated murine macrophages and human gingival fibroblasts (HGF) in vitro. Furthermore, HEK 293 cells transfected with human TLR-9 were also stimulated with these DNA preparations. We observed that DNA from these pathogens stimulates macrophages and gingival fibroblasts to produce tumor necrosis factor alpha and interleukin-6 in a dose-dependent manner. Methylation of the CpG motifs abolished the observed effects. Activation of HEK 293 cells expressing TLR-9 which were responsive to bDNA but not to lipopolysaccharide confirmed that immunostimulation was achieved by bDNA. In addition, the examined bDNA differed in the ability to stimulate murine macrophages, HGF, and TLR-9-transfected cells. DNA from A. actinomycetemcomitans elicited a potent cytokine response, while DNA from P. gingivalis and P. micros showed lower immunostimulatory activity. Taken together, the results strongly suggest that DNA from A. actinomycetemcomitans, P. gingivalis, and P. micros possesses immunostimulatory properties in regard to cytokine secretion by macrophages and fibroblasts. These stimulatory effects are due to unmethylated CpG motifs within bDNA and differ between distinct periodontopathogenic bacteria strains. Hence, immunostimulation by DNA from A. actinomycetemcomitans, P. gingivalis, and P. micros could contribute to the pathogenesis of periodontal diseases.

* Corresponding author. Mailing address: Institute of Medical Microbiology and Hygiene, Philipps University, Pilgrimstein 2, D-35037 Marburg, Germany. Phone: 49 6421 286-6453. Fax: 49 6421 286-6420. E-mail: heeg{at}post.med.uni-marburg.de.

Editor: J. D. Clements

Infection and Immunity, February 2003, p. 850-856, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.850-856.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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