Binding of Toxoplasma gondii Glycosylphosphatidylinositols to Galectin-3 Is Required for Their Recognition by Macrophages

作者：Debierre Grockiego Francoise^*; Niehus Sebastian; Coddeville Bernadette; Elass Elisabeth; Poirier Francoise; Weingart Ralf; Schmidt Richard R; Mazurier Joel; Guerardel Yann; Schwarz Ralph T

来源：Journal of Biological Chemistry, 2010, 285(43): 32744-32750.

DOI：10.1074/jbc.M110.137588

We showed that the production of tumor necrosis factor (TNF) alpha by macrophages in response to Toxoplasma gondii glycosylphosphatidylinositols (GPIs) requires the expression of both Toll-like receptors TLR2 and TLR4, but not of their coreceptor CD14. Galectin-3 is a beta-galactoside-binding protein with immune-regulatory effects, which associates with TLR2. We demonstrate here by using the surface plasmon resonance method that the GPIs of T. gondii bind to human galectin-3 with strong affinity and in a dose-dependent manner. The use of a synthetic glycan and of the lipid moiety cleaved from the GPIs shows that both parts are involved in the interaction with galectin-3. GPIs of T. gondii also bind to galectin-1 but with a lower affinity and only through the lipid moiety. At the cellular level, the production of TNF-alpha induced by T. gondii GPIs in macrophages depends on the expression of galectin-3 but not of galectin-1. This study is the first identification of a galectin-3 ligand of T. gondii origin, and galectin-3 might be a co-receptor presenting the GPIs to the TLRs on macrophages.

• 出版日期2010-10-22