title: Cutting edge: bacterial lipoprotein induces endotoxin-independent tolerance to septic shock.
abstract: Tolerance to bacterial cell wall components is an adaptive host response. Endotoxin/LPS tolerance is characterized by a survival advantage against subsequent lethal LPS challenge. However, it is uncertain whether LPS tolerance can afford protection against other septic challenges. In this study, we show that tolerance induced by bacterial lipoprotein (BLP) protects mice against not only BLP-induced lethality, but also LPS-, live bacteria-, and polymicrobial sepsis-induced lethality. In contrast, LPS tolerance offers no survival benefit against the latter two challenges. Furthermore, induction of BLP tolerance results in overexpression of complement receptor type 3 and FcgammaIII/IIR on neutrophils (polymorphonuclear neutrophils) and peritoneal macrophages, with increased bacterial recognition and bactericidal activity, whereas LPS-tolerized mice exhibit an impaired ability to ingest and to kill bacteria. These results indicate that BLP tolerance is a novel adaptive host response associated with a unique protective effect during septic shock.
authors.affiliation: Department of Academic Surgery, National University of Ireland, Cork University Hospital, Cork, Ireland. jh.wang@ucc.ie
authors.forename: Jiang Huai
authors.initials: JH
authors.lastname: Wang
authors.forename: Majella
authors.initials: M
authors.lastname: Doyle
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Manning
authors.forename: Siobhan
authors.initials: S
authors.lastname: Blankson
authors.forename: Qiong Di
authors.initials: QD
authors.lastname: Wu
authors.forename: Colm
authors.initials: C
authors.lastname: Power
authors.forename: Ronan
authors.initials: R
authors.lastname: Cahill
authors.forename: H Paul
authors.initials: HP
authors.lastname: Redmond
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D001770:Blood Bactericidal Activity / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000276:immunology; D008074:Lipoproteins / Q000008:administration & dosage* / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D008074:Lipoproteins