Published online before print August 8, 2006
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Department Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee
1 Correspondence: Department Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, MSB 501B, Memphis, TN 38163. E-mail: fre{at}utmem.edu
ABSTRACT
Francisella tularensis, a gram-negative, facultative, intracellular bacterium, is the etiologic agent of tularemia and a category A bioterrorism agent. Little is known about the mechanism of pathogenesis of tularemia. In this paper, we describe the interaction of the live vaccine strain of F. tularensis with the innate immune system. We have found that in human and mouse dendritic cells, F. tularensis elicited a powerful inflammatory response, characterized by production of a number of cytokines and chemokines. Using cells derived from TLR2-deficient mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein. F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL-1ß secretion, a reflection of caspase-1 activation, was induced by live but not heat-killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL-1ß transcript. Our results identified activation of TLR2 and caspase-1 as the two main cellular pathways responsible for the inflammatory response to F. tularensis.
Key Words: Toll-like receptors • inflammation • dendritic cells • bacterial infection
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