Basis for the failure of Francisella tularensis lipopolysaccharide to prime human polymorphonuclear leukocytes.
Francisella tularensis is the intracellular gram-negative coccobacillus that causes tularemia, and its virulence and infectiousness make it a potential agent of bioterrorism. Previous studies using mononuclear leukocytes have shown that the lipopolysaccharide (LPS) of F. tularensis is neither a typical proinflammatory endotoxin nor an endotoxin antagonist. This inertness suggests that F. tularensis LPS does not bind host LPS-sensing molecules such as LPS-binding protein (LBP). Using priming of the polymorphonuclear leukocyte (PMN) oxidase as a measure of endotoxicity, we found that F. tularensis live vaccine strain LPS did not behave like either a classic endotoxin or an endotoxin antagonist in human PMNs, even when the concentration of LBP was limiting. Furthermore, F. tularensis LPS did not compete with a radiolabeled lipooligosaccharide from Neisseria meningitidis for binding to LBP or to the closely related PMN granule protein, bactericidal/permeability-increasing protein. Our results suggest that the inertness of F. tularensis LPS and the resistance of F. tularensis to oxygen-independent PMN killing may result from the inability of F. tularensis LPS to be recognized by these important LPS-sensing molecules of the innate immune system.
Barker
Jason H
JH
Inflammation Program and Department of Medicine, University of Iowa, D160 MTF, 2501 Crosspark Road, Coralville, IA, 52241, USA.
Weiss
Jerrold
J
Apicella
Michael A
MA
Nauseef
William M
WM
D000209:Acute-Phase Proteins / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D005604:Francisella tularensis / Q000472:pathogenicity*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000099231:Lipopolysaccharide-Binding Protein; C021623:bactericidal permeability increasing protein; C023023:lipid-linked oligosaccharides