title: A critical role of CpG motifs in a murine peritonitis model by their binding to highly expressed toll-like receptor-9 on liver NKT cells.
abstract: BACKGROUND
  Toll-like receptor (TLR)-9 plays a critical role in the recognition of the CpG motifs, which is frequently observed in bacterial DNA. To date, there have not been any reports regarding the role of bacterial DNA in the systemic circulation on the development of sepsis.
  
  
  METHODS
  We examined the expression of TLR-9 in the liver and spleen in a murine peritonitis model (CLP mice). We also measured the cytokine response of mononuclear cells (MNCs) from normal and CLP mice to CpG oligodeoxynucleotides (ODN) in vitro and in vivo.
  
  
  RESULTS
  TLR-9 expression on F4/80(+) and NK1.1(+)CD3epsilon(+) cells in the liver of CLP mice was elevated compared to sham-operated mice. With regard to cytokine production, we found that CpG ODN markedly stimulated the production of inflammatory cytokines by murine macrophages and liver MNCs. The intravenous injection of CpG ODN in mice that underwent CLP 12h earlier led to their increased cytokine production and their increased mortality. In addition, the depletion of NK/NKT cells contributed to improve their survival rate.
  
  
  CONCLUSIONS
  Our results suggest that, in patients with overwhelming bacterial infection, bacterial DNA may induce liver toxicity that is mediated by liver NKT cells and macrophages that express high levels of TLR-9.
authors.affiliation: Department of Surgery I, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. Tsujiflorida@aol.com
authors.forename: Hironori
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ono
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Kawabata
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Takashi
authors.initials: T
authors.lastname: Majima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hiraki
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology; D020816:Amino Acid Motifs; D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015870:Gene Expression; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D010538:Peritonitis / Q000378:metabolism* / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9