Frontiers in Immunology (Aug 2017)

Class A CpG Oligonucleotide Priming Rescues Mice from Septic Shock via Activation of Platelet-Activating Factor Acetylhydrolase

  • Yoshinari Yamamoto,
  • Yoshinari Yamamoto,
  • Ryu Sugimura,
  • Takafumi Watanabe,
  • Suguru Shigemori,
  • Suguru Shigemori,
  • Takuma Okajima,
  • Shireen Nigar,
  • Shireen Nigar,
  • Fu Namai,
  • Takashi Sato,
  • Tasuku Ogita,
  • Takeshi Shimosato,
  • Takeshi Shimosato

DOI
https://doi.org/10.3389/fimmu.2017.01049
Journal volume & issue
Vol. 8

Abstract

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Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF) induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A1585) strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A1585 rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation. Furthermore, CpG-A1585 improved endotoxin shock induced by lipopolysaccharide, which comprises the cell wall of Gram-negative bacteria and inhibits inflammatory responses induced by cytokines such as interleukin-6 and tumor necrosis factor-α. These results suggest that CpG-A1585 is a potential therapeutic target to prevent sepsis-related induction of PAF.

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