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Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

2015; Cell Press; Volume: 10; Issue: 9 Linguagem: Inglês

10.1016/j.celrep.2015.02.012

2639-1856

Miguel Ángel Burguillos, Martina Svensson, Tim Schulte, Antonio Boza‐Serrano, Albert García-Quintanilla, Edel Kavanagh, Martiniano Santiago, Nikenza Viceconte, Maria José Oliva-Martín, Ahmed M. Osman, Emma Salomonsson, Lahouari Amar, Annette Persson, Klas Blomgren, Adnane Achour, Elisabet Englund, Hakon Leffler, José L. Venero, Bertrand Joseph, Tomas Deierborg,

Signaling Pathways in Disease

Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.