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CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species
Journal article   Peer reviewed

CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species

Ae-Kyung Yi, Rebecca Tuetken, Thomas Redford, Marianella Waldschmidt, Jeffrey Kirsch and Arthur M Krieg
The Journal of immunology (1950), Vol.160(10), pp.4755-4761
05/15/1998
DOI: 10.4049/jimmunol.160.10.4755
PMID: 9590221

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Abstract

B cells and monocytes endocytose DNA into an acidified intracellular compartment. If this DNA contains unmethylated CpG dinucleotides in particular base contexts (CpG motifs), these leukocytes are rapidly activated. We now show that both B cell and monocyte-like cell line responses to DNA containing CpG motifs (CpG DNA) are sensitive to endosomal acidification inhibitors; they are completely blocked by bafilomycin A, chloroquine, and monensin. The specificity of these inhibitors is demonstrated by their failure to prevent responses to LPS, PMA, or ligation of CD40 or IgM. Acidification of endosomal CpG DNA is coupled to the rapid generation of intracellular reactive oxygen species. The CpG DNA-induced reactive oxygen species burst is linked to the degradation of IkappaB and the activation of NFkappaB, which induces leukocyte gene transcription and cytokine secretion. These studies demonstrate a novel pathway of leukocyte activation triggered by CpG motifs.
 DNA, Bacterial - pharmacology NF-KappaB Inhibitor alpha Reactive Oxygen Species Cytokines - secretion I-kappa B Proteins NF-kappa B - metabolism DNA-Binding Proteins - metabolism Chloroquine - pharmacology Animals Leukocytes - drug effects Mice, Inbred DBA Mice Dinucleoside Phosphates - pharmacology Leukocytes - metabolism Hydrogen-Ion Concentration

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