Bacterial Peptidoglycan-Associated Lipoprotein: A Naturally Occurring Toll-Like Receptor 2 Agonist That Is Shed into Serum and Has Synergy with Lipopolysaccharide

• Published in: The Journal of infectious diseases Vol. 191; no. 6; pp. 939 - 948
• Main Authors: Liang, Michael D., Bagchi, Aranya, Warren, H. Shaw, Tehan, Megan M., Trigilio, James A., Beasley-Topliffe, Laura K., Tesini, Brenda L., Lazzaroni, Jean-Claude, Fenton, Matthew J., Hellman, Judith
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.03.2005; University of Chicago Press; Oxford University Press
• Subjects: Agonists; Animals; Bacteria; Bacterial Outer Membrane Proteins - blood; Bacterial Outer Membrane Proteins - immunology; Bacteriology; Biological and medical sciences; Cell Line; Cytokines; Drug Synergism; Escherichia coli; Escherichia coli - immunology; Escherichia coli K12 - immunology; Escherichia coli Proteins; Fundamental and applied biological sciences. Psychology; Humans; Infectious diseases; Lipopolysaccharides; Lipopolysaccharides - immunology; Lipoproteins; Lipoproteins - blood; Lipoproteins - immunology; Macrophage Activation; Macrophages; Macrophages, Peritoneal - immunology; Medical sciences; Membrane Glycoproteins - agonists; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Miscellaneous; Peptidoglycan - blood; Peptidoglycan - immunology; Receptors, Cell Surface - agonists; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Sepsis; Sepsis - physiopathology; Toll like receptors; Toll-Like Receptor 2; Transfection; Infection; Peptidoglycan; Microbiology; Lipopolysaccharide; Bacteria; Serum; Toll like receptor; Lipoprotein
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/427815

Sepsis is initiated by interactions between microbial products and host inflammatory cells. Toll-like receptors (TLRs) are central innate immune mediators of sepsis that recognize different components of microorganisms. Peptidoglycan-associated lipoprotein (PAL) is a ubiquitous gram-negative bacterial outer-membrane protein that is shed by bacteria into the circulation of septic animals. We explored the inflammatory effects of purified PAL and of a naturally occurring form of PAL that is shed into serum. PAL is released into human serum by Escherichia coli bacteria in a form that induces cytokine production by macrophages and is tightly associated with lipopolysaccharide (LPS). PAL activates inflammation through TLR2. PAL and LPS synergistically activate macrophages. These data suggest that PAL may play an important role in the pathogenesis of sepsis and imply that physiologically relevant PAL and LPS are shed into serum and act in concert to initiate inflammation in sepsis