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

Miguel Angel Burguillos; Martina Svensson; Tim Schulte; Antonio Boza-Serrano; Albert Garcia-Quintanilla; Edel Kavanagh; Martiniano Santiago; Nikenza Viceconte; Maria Jose Oliva-Martin; Ahmed Mohamed Osman; Emma Salomonsson; Lahouari Amar; Annette Persson; Klas Blomgren; Adnane Achour; Elisabet Englund; Hakon Leffler; Jose Luis Venero; Bertrand Joseph; Tomas Deierborg

doi:10.1016/j.celrep.2015.02.012

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

Cell Rep. 2015 Mar 10;10(9):1626-1638. doi: 10.1016/j.celrep.2015.02.012. Epub 2015 Mar 5.

Authors

Miguel Angel Burguillos¹, Martina Svensson², Tim Schulte³, Antonio Boza-Serrano², Albert Garcia-Quintanilla⁴, Edel Kavanagh⁵, Martiniano Santiago⁴, Nikenza Viceconte⁴, Maria Jose Oliva-Martin⁴, Ahmed Mohamed Osman⁶, Emma Salomonsson⁷, Lahouari Amar⁸, Annette Persson⁹, Klas Blomgren⁶, Adnane Achour³, Elisabet Englund⁹, Hakon Leffler⁷, Jose Luis Venero⁴, Bertrand Joseph⁵, Tomas Deierborg²

Affiliations

¹ Department of Oncology-Pathology, Cancer Centrum Karolinska, R8:03, Karolinska Institutet, Stockholm 171 76, Sweden; Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, Lund 221 84, Sweden. Electronic address: m.burguillos@qmul.ac.uk.
² Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, Lund 221 84, Sweden.
³ Science for Life Laboratory, Department of Medicine Solna, Karolinska Institutet, Stockholm 17165, Sweden.
⁴ Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla 41012, Spain.
⁵ Department of Oncology-Pathology, Cancer Centrum Karolinska, R8:03, Karolinska Institutet, Stockholm 171 76, Sweden.
⁶ Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Q2:07, Stockholm 171 76, Sweden.
⁷ Section MIG, Department of Laboratory Medicine, Solvegatan 23, Lund University, Lund 223 62, Sweden.
⁸ Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund 221 84, Sweden.
⁹ Department of Pathology, Division of Neuropathology, Lund University Hospital, Lund 221 85, Sweden.

PMID: 25753426
DOI: 10.1016/j.celrep.2015.02.012

Abstract

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.