CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract.

Abstract

Since unmethylated CpG motifs are more frequent in DNA from bacteria than vertebrates, and the unmethylated CpG motif has recently been reported to have stimulatory effects on lymphocytes, we speculated that bacterial DNA may induce inflammation in the lower respiratory tract through its content of unmethylated CpG motifs. To determine the role of bacterial DNA in lower airway inflammation, we intratracheally instilled prokaryotic and eukaryotic DNA in C3H/HeBFEJ mice and performed whole lung lavage 4 h after the exposure. Heat denatured, single stranded Escherichia coli genomic DNA (0.06 ng endotoxin/ g DNA) was compared to heat denatured, single stranded calf thymus DNA (

CpG DNA and LPS induce distinct patterns of activation in human monocytes

“…48 Recently it was shown that CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract suggesting that CpG DNA may play an important pathogenic role in inflammatory lung disease. 49 In chronic inflammatory bowel disease, the loss of the mucosal integrity could expose immune cells to both LPS and bacterial DNA present at high levels in the lumen of the bowel. This may trigger periodic aggravation of the disease.…”

LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth

“…It is well established that bacterial DNA can initiate a potent inflammatory cytokine response following localized injection (intramuscular, subcutaneous, intraperitoneal or intra-tumor) [7][8][9][10][11][12][13] or intratracheal instillation. 14,15 It appears that unmethylated CpG sequences, occurring at higher frequency in bacterial DNA compared with vertebrate DNA, are responsible for inducing the cytokine response (reviewed by Kreig). 16 Indeed, both bacterial DNA and oligonucleotides (ODN) containing immune-stimulatory CpG motifs can directly stimulate macrophages 10,17 and dendritic cells 18,19 for the production of TNF-␣ and IL-12.…”

Bacterial DNA is implicated in the inflammatory response to delivery of DNA/DOTAP to mouse lungs

“…2 It has recently been reported that instillation of bacterial DNA causes inflammation in the lower respiratory tract of rodents. This was ascribable to the increased number and unmethylated status of bacterial CpG motifs 3 particularly when present in a particular base context. 4 response.…”

“…3 It was suggested that the immune system recognises this molecular pattern as 'foreign' thus activating appropriate immune responses.…”