Effects of Toll-like Receptor 2 and Toll-like Receptor 4 in Toxoplasma Gondii-Derived Heat Shock Protein 70-induced Tolerance in Nitric Oxide Production

摘要

Peritoneal macrophages (PMs) from toll-like receptor (TLR) 4-deficient and wild type (WT) mice were responsive to Toxoplasma gondii-derived heat shock protein 70 (TgHSP70) in nitric oxide (NO) release, but those from TLR2-, myeloid differentiation factor 88 (MyD88)-, and IL-1R-associated kinase (IRAK) 4-deficient mice were not. Pretreatment of PMs from WT but not from TLR4-deficient mice with TgHSP70 resulted in suppression of NO release on restimulation with TgHSP70. Furthermore, PMs from WT but not from TLR4-deficient mice increased the suppressor of cytokine-signaling-1 (SOCS-1) expression after restimulation with TgHSP70. Phosphorylation of I-kappaBAlppa occurred in TgHSP70-induced tolerance of PMs from TLR4-deficient but not from WT mice. These data indicated that TgHSP70 signaling mechanisms in NO release were mediated by TLR2, MyD88 and IRAK4, but not by TLR4. On the other hand, signaling of TgHSP70-induced tolerance was mediated by TLR4, and the expression of SOCS-1 suppressed the TLR2 signaling pathway.