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The actions of bacterial DNA on murine macrophages
Author(s) -
Sester David P.,
Stacey Katryn J.,
Sweet Matthew J.,
Beasley Shan J.,
Cronau Stephen L.,
Hume David A.
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.4.542
Subject(s) - biology , cpg site , microbiology and biotechnology , cpg oligodeoxynucleotide , dna damage , cytokine , toll like receptor 9 , dna , oligonucleotide , gene , immunology , genetics , gene expression , dna methylation
Murine macrophages are able to distinguish bacterial from mammalian DNA. The response is mimicked by single‐stranded oligonucleotides containing unmethylated CG dinucleotides (“CpG” motifs) in specific sequence contexts. The dose‐response curve for activation is influenced by variation in the sequence flanking the core CpG motif. CpG or bacterial DNA activates several signaling pathways in common with bacterial lipopolysaccharide (LPS), leading to induction of cytokine genes such as tumor necrosis factor a. Pretreatment with LPS causes desensitization to subsequent activation by CpG DNA. Both stimuli also cause cell cycle arrest in macrophages proliferating in response to the macrophage growth factor colony‐stimulating factor‐1 (CSF‐1), but prevent apoptosis caused by growth factor removal. In part, cell cycle arrest by CpG DNA and LPS may be linked to rapid down‐modulation of the CSF‐1 receptor from the cell surface, a response that occurs in an all‐or‐nothing manner. The response of macrophages to CpG DNA has aspects in common with the DNA damage response in other cell types, which may provide clues to the underlying mechanism. J. Leukoc. Biol. 66: 542–548; 1999.