Open AccessInterleukin‐18 secretion and Th1‐like cytokine responses in human peripheral blood mononuclear cells under the influence of the toll‐like receptor‐5 ligand flagellin
Author(s) -
Bachmann Malte,
Horn Katharina,
Poleganov Marco A.,
Paulukat Jens,
Nold Marcel,
Pfeilschifter Josef,
Mühl Heiko
Publication year - 2006
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2005.00621.x
Subject(s) - peripheral blood mononuclear cell , biology , flagellin , toll like receptor , immunology , secretion , cytokine , peripheral blood , common gamma chain , receptor , toll , immune system , interleukin 10 , endocrinology , innate immune system , in vitro , biochemistry
Summary Flagellin is the major protein component of the flagella from motile bacteria and was identified as the ligand for toll‐like receptor (TLR)‐5. Whereas its effects on epithelial cells have been studied in detail, activation of human peripheral blood mononuclear cells (PBMC) by flagellin is characterized only partially. By using the recombinant protein of Salmonella muenchen we confirm the proinflammatory nature of flagellin as detected by nuclear factor‐κB activation and interleukin (IL)‐8 production. Aim of the current study was to elucidate in PBMC effects of flagellin on IL‐18 and Th1‐like cytokine responses. We report that flagellin in pathophysiologically relevant concentrations augmented release of mature IL‐18 by THP‐1 monocytes, PBMC, and whole blood stimulated with nigericin or by ATP‐mediated P2X 7 purinergic receptor activation. Further key functions of the IL‐18/IL‐12/interferon‐γ (IFNγ) pathway were upregulated by flagellin. Flagellin synergized with IL‐12 for production of IFN‐γ and augmented secretion of interferon‐inducible protein‐10, a CXC‐chemokine that is key to the generation of Th1‐type responses. In contrast, neither IL‐18‐binding protein nor IL‐4 was affected. Taken together, the present data demonstrate for the first time that flagellin at concentrations that are detectable in the blood compartment during sepsis efficiently enhances the IL‐18/IL‐12/IFNγ pathway and thus Th1‐like cytokine responses in PBMC.