Binding of Toxoplasma gondii glycosylphosphatidylinositols to galectin-3 is required for their recognition by macrophages.
We showed that the production of tumor necrosis factor (TNF) α by macrophages in response to Toxoplasma gondii glycosylphosphatidylinositols (GPIs) requires the expression of both Toll-like receptors TLR2 and TLR4, but not of their co-receptor CD14. Galectin-3 is a β-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-α 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.
Debierre-Grockiego
Françoise
F
From the Institut für Virologie, AG Parasitologie, Philipps University, Marburg D-35043, Germany; Unité Mixte de Recherche Université-Institut National de la Recherche Agronomique 0483 Immunologie Parasitaire, Vaccinologie et Biothérapies Anti-infectieuses, Unité de Formation de Recherche Sciences Pharmaceutiques, 31 Avenue Monge, F-37200 Tours, France. Electronic address: francoise.debierre@univ-tours.fr.
Niehus
Sebastian
S
From the Institut für Virologie, AG Parasitologie, Philipps University, Marburg D-35043, Germany.
Coddeville
Bernadette
B
CNRS-Unité Mixte de Recherche 8576, Unit of Structural and Functional Glycobiology, Institut Fédératif de Recherche 147, Université Lille Nord de France, F-59000 Lille, France.
Elass
Elisabeth
E
CNRS-Unité Mixte de Recherche 8576, Unit of Structural and Functional Glycobiology, Institut Fédératif de Recherche 147, Université Lille Nord de France, F-59000 Lille, France.
Poirier
Françoise
F
Laboratoire de Génétique et Développement des Mammifères, Institut Jacques Monod, Paris F-75013, France.
Weingart
Ralf
R
Fachbereich Chemie, University of Konstanz, Konstanz D-78457, Germany.
Schmidt
Richard R
RR
Fachbereich Chemie, University of Konstanz, Konstanz D-78457, Germany.
Mazurier
Joël
J
CNRS-Unité Mixte de Recherche 8576, Unit of Structural and Functional Glycobiology, Institut Fédératif de Recherche 147, Université Lille Nord de France, F-59000 Lille, France.
Guérardel
Yann
Y
CNRS-Unité Mixte de Recherche 8576, Unit of Structural and Functional Glycobiology, Institut Fédératif de Recherche 147, Université Lille Nord de France, F-59000 Lille, France.
Schwarz
Ralph T
RT
From the Institut für Virologie, AG Parasitologie, Philipps University, Marburg D-35043, Germany; CNRS-Unité Mixte de Recherche 8576, Unit of Structural and Functional Glycobiology, Institut Fédératif de Recherche 147, Université Lille Nord de France, F-59000 Lille, France.
D000818:Animals; D002522:Chlorocebus aethiops; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014122:Toxoplasma / Q000378:metabolism*; D014709:Vero Cells
D037483:Galectin 1; D037502:Galectin 3; D017261:Glycosylphosphatidylinositols; C485095:Lgals3 protein, mouse; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4