The Essential Role of Lipopolysaccharide-Binding Protein in Protection of Mice Against a Peritoneal Salmonella Infection Involves the Rapid Induction of an Inflammatory Response

• Published in: The Journal of immunology (1950) Vol. 167; no. 3; pp. 1624 - 1628
• Main Authors: Heinrich, Jan-Michael, Bernheiden, Martin, Minigo, Gabriela, Yang, Kang Kang, Schutt, Christine, Mannel, Daniela N, Jack, Robert S
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.08.2001
• Subjects: Acute-Phase Proteins; Animals; Carrier Proteins - administration & dosage; Carrier Proteins - genetics; Carrier Proteins - physiology; Genetic Predisposition to Disease; Humans; Injections, Intraperitoneal; LBP protein; Lipopolysaccharides - metabolism; Lung - microbiology; Lung - pathology; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Knockout; Peritoneum - microbiology; Peritoneum - pathology; Peritonitis - genetics; Peritonitis - immunology; Peritonitis - pathology; Peritonitis - prevention & control; Phenotype; Recombinant Proteins - administration & dosage; Salmonella; Salmonella Infections, Animal - genetics; Salmonella Infections, Animal - immunology; Salmonella Infections, Animal - pathology; Salmonella Infections, Animal - prevention & control; Salmonella typhimurium - growth & development; Salmonella typhimurium - immunology; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - therapeutic use
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.3.1624

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.