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Infection and Immunity, June 2006, p. 3277-3284, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.02011-05

Basis for the Failure of Francisella tularensis Lipopolysaccharide To Prime Human Polymorphonuclear Leukocytes

Inflammation Program and Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa and Veterans Administration Medical Center,¹ Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa²

Received 14 December 2005/ Returned for modification 23 January 2006/ Accepted 27 February 2006

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.

Editor: J. T. Barbieri

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