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Lipopolysaccharide-binding protein is required to combat a murine Gram-negative bacterial infection

Abstract

An invading pathogen must be held in check by the innate immune system until a specific immune response can be mounted. In the case of Gram-negative bacteria, the principal stimulator of the innate immune system is lipopolysaccharide (LPS), a component of the bacterial outer membrane1. In vitro, LPS is bound by lipopolysaccharide-binding protein (LBP)2 and transferred to CD14—the LPS receptor on the macrophage surface3,4—or to high-density lipoprotein (HDL) particles5,6. Transfer to CD14 triggers an inflammatory response which is crucial for keeping an infection under control. Here we investigate how LBP functions in vivo by using LBP-deficient mice. Surprisingly, we find that LBP is not required in vivo for the clearance of LPS from thecirculation, but is essential for the rapid induction of an inflammatory response by small amounts of LPS or Gram-negative bacteria and for survival of an intraperitoneal Salmonella infection.

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Figure 1: Maps of the mouse genomic clone containing three exons of the LBP gene (top), the targeting vector (middle) and the expected structure of the recombinant chromosome (lower).
Figure 2: FACS analysis of LBP-mediated transfer of FITC-labelled LPS to CHO cells expressing mouse CD14.
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Correspondence to Robert S. Jack.

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Jack, R., Fan, X., Bernheiden, M. et al. Lipopolysaccharide-binding protein is required to combat a murine Gram-negative bacterial infection. Nature 389, 742–745 (1997). https://doi.org/10.1038/39622

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