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.
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Animals
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Bacterial Outer Membrane Proteins / administration & dosage*
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Bacterial Outer Membrane Proteins / immunology
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Blood Bactericidal Activity / immunology
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Cytokines / antagonists & inhibitors
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Cytokines / biosynthesis
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Immune Tolerance / immunology*
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Inflammation / immunology
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Inflammation / prevention & control
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Injections, Intraperitoneal
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Lipopolysaccharides / administration & dosage*
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Lipopolysaccharides / immunology
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Lipoproteins / administration & dosage*
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Lipoproteins / immunology
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Macrophage Activation / immunology
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism
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Macrophages, Peritoneal / microbiology
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Male
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Mice
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Mice, Inbred C57BL
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Neutrophil Activation / immunology
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Neutrophils / immunology
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Neutrophils / metabolism
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Neutrophils / microbiology
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Shock, Septic / immunology*
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Shock, Septic / mortality
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Shock, Septic / prevention & control
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Survival Analysis
Substances
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Adjuvants, Immunologic
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Bacterial Outer Membrane Proteins
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Cytokines
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Lipopolysaccharides
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Lipoproteins