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

• Published in: Cell reports (Cambridge) Vol. 10; no. 9; pp. 1626 - 1638
• Main Authors: Burguillos, Miguel Angel, Svensson, Martina, Schulte, Tim, Boza-Serrano, Antonio, Garcia-Quintanilla, Albert, Kavanagh, Edel, Santiago, Martiniano, Viceconte, Nikenza, Oliva-Martin, Maria Jose, Osman, Ahmed Mohamed, Salomonsson, Emma, Amar, Lahouari, Persson, Annette, Blomgren, Klas, Achour, Adnane, Englund, Elisabet, Leffler, Hakon, Venero, Jose Luis, Joseph, Bertrand, Deierborg, Tomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.03.2015; Elsevier
• Subjects: Biologi; Biological Sciences; Cell Biology; Cellbiologi; Natural Sciences; Naturvetenskap
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.02.012

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. [Display omitted] •Gal3 acts as an endogenous TLR4 ligand with a Kd value around 1 μM•Gal3 can initiate a TLR4-dependent inflammatory response in microglia•Gal3 is required for complete activation of TLR4 upon LPS treatment•Gal3-TLR4 interaction is confirmed in vivo and in stroke patients In this publication, Burguillos et al. demonstrate how galectin-3 (Gal3) released from reactive microglia cells can activate other surrounding immune cells in a paracrine manner by binding to and activating Toll-like receptor 4 (TLR4). This finding could explain the propagation of the inflammatory response once the initial stimulus is gone.