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, Arthur M. Krieg

Research output: Contribution to journalArticle

269 Citations (Scopus)

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 IκB and the activation of NFκB, which induces leukocyte gene transcription and cytokine secretion. These studies demonstrate a novel pathway of leukocyte activation triggered by CpG motifs.

Original languageEnglish (US)
Pages (from-to)4755-4761
Number of pages7
JournalJournal of Immunology
Volume160
Issue number10
StatePublished - May 15 1998
Externally publishedYes

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Bacterial DNA
Reactive Oxygen Species
Leukocytes
DNA
Monocytes
B-Lymphocytes
Monensin
Nucleotide Motifs
Chloroquine
Endocytosis
Ligation
Immunoglobulin M
Cytokines
Cell Line
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Yi, A-K., Tuetken, R., Redford, T., Waldschmidt, M., Kirsch, J., & Krieg, A. M. (1998). CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. Journal of Immunology, 160(10), 4755-4761.

CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. / Yi, Ae-Kyung; Tuetken, Rebecca; Redford, Thomas; Waldschmidt, Marianella; Kirsch, Jeffrey; Krieg, Arthur M.

In: Journal of Immunology, Vol. 160, No. 10, 15.05.1998, p. 4755-4761.

Research output: Contribution to journalArticle

Yi, A-K, Tuetken, R, Redford, T, Waldschmidt, M, Kirsch, J & Krieg, AM 1998, 'CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species', Journal of Immunology, vol. 160, no. 10, pp. 4755-4761.
Yi A-K, Tuetken R, Redford T, Waldschmidt M, Kirsch J, Krieg AM. CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. Journal of Immunology. 1998 May 15;160(10):4755-4761.
Yi, Ae-Kyung ; Tuetken, Rebecca ; Redford, Thomas ; Waldschmidt, Marianella ; Kirsch, Jeffrey ; Krieg, Arthur M. / CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. In: Journal of Immunology. 1998 ; Vol. 160, No. 10. pp. 4755-4761.
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