Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1

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 de-scribe 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 re-sponse, 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 me-diated by TLR2 and did not require the LPS-bind-ing protein. F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL-1 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-1 transcript. Our results identified activation of TLR2 and caspase-1 as the two main cellular pathways responsible for the in-flammatory response to F. tularensis. J. Leukoc