Cutting edge: natural DNA repetitive extragenic sequences from gram-negative pathogens strongly stimulate TLR9.
Bacterial DNA exerts immunostimulatory effects on mammalian cells via the intracellular TLR9. Although broad analysis of TLR9-mediated immunostimulatory potential of synthetic oligonucleotides has been developed, which kinds of natural bacterial DNA sequences are responsible for immunostimulation are not known. This work provides evidence that the natural DNA sequences named repetitive extragenic palindromic (REPs) sequences present in Gram-negative bacteria are able to produce innate immune system stimulation via TLR9. A strong induction of IFN-alpha production by REPs from Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and Neisseria meningitidis was detected in splenocytes from 129 mice. In addition, the involvement of TLR9 in immune stimulation by REPs was confirmed using B6.129P2-Tlr9(tm1Aki) knockout mice. Considering the involvement of TLRs in Gram-negative septic shock, it is conceivable that REPs play a role in its pathogenesis. This study highlights REPs as a potential novel target in septic shock treatment.
Magnusson
Mattias
M
Department of Rheumatology and Inflammation Research, Göteborg University, Göteborg, Sweden.
Tobes
Raquel
R
Sancho
Jaime
J
Pareja
Eduardo
E
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000378:metabolism / Q000502:physiology*; D048168:Escherichia coli K12 / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012485:Salmonella typhi / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D004269:DNA, Bacterial; D008024:Ligands; D051217:Toll-Like Receptor 9