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Accumulating evidence suggests that parasites is inflammatorily active in liver, but the molecular mechanism(s) through which parasites modulates the hepatic innate immune system has not been clearly elucidated. In this study, we found that Toxoplasma gondii profilin, a ligand of toll-like receptor 11 (TLR11), induced the fulminant hepatitis in D-GalN-sensitized mice. The levels of inflammatory cytokine TNFα, IFN-γ and IL-12 in the serum were significantly increased following administration of profilin and D-GalN. Neutralization of these cytokine completely abolished profilin/GalN-induced liver injury. Profilin/GalN treatment could induce recruitment and activation of Kupffer cells and NK cells in liver. TNFα and IFN-γ were produced by Kupffer cells and NK cells, respectively, in profilin/GalN treated mice. Moreover, depletion of Kuppfer cells or NK cells could protect mice from profilin/GalN-induced liver injury, suggesting that these innate immune cells were the major sources of those inflammatory cytokines. This is the first report to show TLR11-induced liver injury, which is helpful to study the liver diseases with parasite infection. |
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Keywords:Toll-like receptor 11;liver injury;Kupffer cells;NK cells;cytokines |
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