title: The essential role of lipopolysaccharide-binding protein in protection of mice against a peritoneal Salmonella infection involves the rapid induction of an inflammatory response.
abstract: Acute and chronic hyperinflammation are of major clinical concern, and many treatment strategies are therefore directed to inactivating parts of the inflammatory system. However, survival depends on responding quickly to pathogen attack, and since the adaptive immune system requires several days to adequately react, we rely initially on a range of innate defenses, many of which operate by activating parts of the inflammatory network. For example, LPS-binding protein (LBP) can transfer the LPS of Gram-negative bacteria to CD14 on the surface of macrophages, and this initiates an inflammatory reaction. However, the importance of this chain of events in infection is unclear. First, the innate system is redundant, and bacteria have many components that may serve as targets for it. Second, LBP can transfer LPS to other acceptors that do not induce inflammation. In this study, we show that innate defense against a lethal peritoneal infection with Salmonella requires a direct proinflammatory involvement of LBP, and that this is a major nonredundant function of LBP in this infection model. This emphasizes that blocking the LBP-initiated inflammatory cascade disables an essential defense pathway. Any anti-inflammatory protection that may be achieved must be balanced against the risks inherent in blinding the innate system to the presence of Gram-negative pathogens.
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Klinikum der Universität Greifswald, Sauerbruchstrasse, D-17489 Greifswald, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Heinrich
authors.forename: M
authors.initials: M
authors.lastname: Bernheiden
authors.forename: G
authors.initials: G
authors.lastname: Minigo
authors.forename: K K
authors.initials: KK
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Schütt
authors.forename: D N
authors.initials: DN
authors.lastname: Männel
authors.forename: R S
authors.initials: RS
authors.lastname: Jack
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000378:metabolism*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010537:Peritoneum / Q000382:microbiology / Q000473:pathology; D010538:Peritonitis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D010641:Phenotype; D011994:Recombinant Proteins / Q000008:administration & dosage; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein