Intra-articularly localized bacterial DNA containing CpG motifs induces arthritis (original) (raw)

Nature Medicine volume 5, pages 702–705 (1999)Cite this article

Abstract

Unmethylated CpG motifs are often found in bacterial DNA, and exert immunostimulatory effects on hematopoetic cells1,2,3. Bacteria produce severe joint inflammation in septic and reactive arthritides; bacterial DNA may be involved in this process. We injected bacterial DNA originating from Escherichia coli and Staphylococcus aureus and oligonucleotides containing CpG directly into the knee joints of mice of different strains. Arthritis was seen by histopathology within 2 hours and lasted for at least 14 days. Unmethylated CpG motifs were responsible for this induction of arthritis, as oligonucleotides containing these motifs produced the arthritis. The arthritis was characterized by an influx of monocytic, Mac-1+ cells and by a lack of T lymphocytes. Depletion of monocytes resulted in abrogation of the synovial inflammation. Tumor necrosis factor (TNF)-α, a cytokine produced by cells of the monocyte/macrophage lineage, is an important mediator of this disease, as expression of mRNA for TNF-α was evident in the inflamed joints, and the CpG-mediated inflammation was abrogated in mice genetically unable to produce this cytokine. These findings demonstrate that bacterial DNA containing unmethylated CpG motifs induces arthritis, and indicate an important pathogenic role for bacterial DNA in septic arthritis.

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Authors and Affiliations

  1. Department of Rheumatology, University of Göteborg, Guldhedsgatan 10A, S-413 46, Göteborg, Sweden
    Guo-Min Deng, Ing-Marie Nilsson, Margareta Verdrengh, L.Vincent Collins & Andrej Tarkowski

Authors

  1. Guo-Min Deng
  2. Ing-Marie Nilsson
  3. Margareta Verdrengh
  4. L.Vincent Collins
  5. Andrej Tarkowski

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Correspondence toGuo-Min Deng.

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Deng, GM., Nilsson, IM., Verdrengh, M. et al. Intra-articularly localized bacterial DNA containing CpG motifs induces arthritis.Nat Med 5, 702–705 (1999). https://doi.org/10.1038/9554

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