Open AccessToll-Like Receptor 2 Is Required for Inflammatory Responses toFrancisella tularensisLVS
Author(s) -
Jannet Katz,
Ping Zhang,
Michael Martin,
Stefanie N. Vogel,
Suzanne M. Michalek
Publication year - 2006
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.74.5.2809-2816.2006
Subject(s) - francisella tularensis , tularemia , tlr2 , biology , toll like receptor , tlr4 , cd80 , microbiology and biotechnology , immunology , tumor necrosis factor alpha , immune system , cd86 , cd40 , innate immune system , t cell , in vitro , cytotoxic t cell , biochemistry , virulence , gene
Francisella tularensis , a gram-negative bacterium, is the etiologic agent of tularemia and has recently been classified as a category A bioterrorism agent. Infections withF. tularensis result in an inflammatory response that plays an important role in the pathogenesis of the disease; however, the cellular mechanisms mediating this response have not been completely elucidated. In the present study, we determined the role of Toll-like receptors (TLRs) in mediating inflammatory responses toF. tularensis LVS, and the role of NF-κB in regulating these responses. Stimulation of bone marrow-derived dendritic cells from C57BL/6 wild-type (wt) and TLR4−/− but not TLR2−/− mice, with liveF. tularensis LVS elicited a dose-dependent increase in the production of tumor necrosis factor alpha.F. tularensis LVS also induced in a dose-dependent manner an up-regulation in the expression of the costimulatory molecules CD80 and CD86 and of CD40 and the major histocompatibility complex class II molecules on dendritic cells from wt and TLR4−/− but not TLR2−/− mice. TLR6, not TLR1, was shown to be involved in mediating the inflammatory response toF. tularensis LVS, indicating that the functional heterodimer is TLR2/TLR6. Stimulation of dendritic cells withF. tularensis resulted in the activation of NF-κB, which resulted in a differential effect on the production of pro- and anti-inflammatory cytokines. Taken together, our results demonstrate the role of TLR2/TLR6 in the host's inflammatory response toF. tularensis LVS in vitro and the regulatory function of NF-κB in modulating the inflammatory response.