Differences in macrophage activation by bacterial DNA and CpG-containing oligonucleotides

Roberts, T. L., Dunn, J. A., Terry, T. D., Jennings, M. P., Hume, D. A., Sweet, M. J. and Stacey, K. J. (2005) Differences in macrophage activation by bacterial DNA and CpG-containing oligonucleotides. Journal of Immunology, 175 6: 3569-3576.

Author Roberts, T. L.
Dunn, J. A.
Terry, T. D.
Jennings, M. P.
Hume, D. A.
Sweet, M. J.
Stacey, K. J.
Title Differences in macrophage activation by bacterial DNA and CpG-containing oligonucleotides
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2005-01-01
Sub-type Article (original research)
Volume 175
Issue 6
Start page 3569
End page 3576
Total pages 8
Place of publication Bethesda
Publisher Amer Assoc Immunologists
Language eng
Subject C1
320202 Cellular Immunology
730102 Immune system and allergy
Abstract Bacterial DNA activates mouse macrophages, B cells, and dendritic cells in a TLR9-dependent manner. Although short ssCpG-containing phosphodiester oligonucleotides (PO-ODN) can mimic the action of bacterial DNA on macrophages, they are much less immunostimulatory than Escherichia coli DNA. In this study we have assessed the structural differences between E. coli DNA and PO-ODN, which may explain the high activity of bacterial DNA on macrophages. DNA length was found to be the most important variable. Double-strandedness was not responsible for the increased activity of long DNA. DNA adenine methyltransferase (Dam) and DNA cytosine methyltransferase (Dcm) methylation of E. coli DNA did not enhance macrophage NO production. The presence of two CpG motifs on one molecule only marginally improved activity at low concentration, suggesting that ligand-mediated TLR9 cross-linking was not involved. The major contribution was from DNA length. Synthetic ODN > 44 nt attained the same levels of activity as bacterial DNA. The response of macrophages to CpG DNA requires endocytic uptake. The length dependence of the CpG ODN response was found to correlate with the presence in macrophages of a length-dependent uptake process for DNA. This transport system was absent from B cells and fibroblasts.
Keyword Immunology
Toll-like Receptor-9
Phosphorothioate Oligodeoxynucleotides
Scavenger Receptor
Peritoneal-macrophages
Immune Stimulation
Binding Protein
Cells
Responses
Lipopolysaccharide
Recognition
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 15:51:45 EST