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

Miguel Burguillos Garcia; 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.

Miguel Burguillos Garcia, 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

Research output: Contribution to journal › Article › peer-review

315 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1626-1638
Journal	Cell Reports
Volume	10
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2015.02.012
Publication status	Published - 2015

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Neuronal Survival (013212041), Pathology, (Lund) (013030000), Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Neuroinflammation (013210006)

Subject classification (UKÄ)

Cell Biology

Access to Document

10.1016/j.celrep.2015.02.012

Cell_reports_Garcia_et_al

http://www.ncbi.nlm.nih.gov/pubmed/25753426?dopt=Abstract

2 Doctoral Thesis (compilation)

Physical exercise as a preventive strategy for disorders affecting the brain. The effect on neuroinflammation.
Svensson, M., 2020, Lund: Lund University, Faculty of Medicine. 132 p.
Research output: Thesis › Doctoral Thesis (compilation)

Open Access
File
Microglial cells in Neurodegenerative Diseases. The Role of Galectin-3
Boza Serrano, A., 2017, Lund: Lund University: Faculty of Medicine. 107 p.
Research output: Thesis › Doctoral Thesis (compilation)

Open Access
File

Cite this

Burguillos Garcia, M., Svensson, M., Schulte, T., Boza Serrano, A., Garcia-Quintanilla, A., Kavanagh, E., Santiago, M., Viceconte, N., Oliva-Martin, M. J., Osman, A. M., Salomonsson, E., Amar, L., Persson, A., Blomgren, K., Achour, A., Englund, E., Leffler, H., Venero, J. L., Joseph, B., & Deierborg, T. (2015). Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation. Cell Reports, 10(9), 1626-1638. https://doi.org/10.1016/j.celrep.2015.02.012

@article{d42d59efb2f946b88066b41ac268f5f6,

title = "Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.",

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.",

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

note = "The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041), Pathology, (Lund) (013030000), Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Neuroinflammation (013210006)",

year = "2015",

doi = "10.1016/j.celrep.2015.02.012",

language = "English",

volume = "10",

pages = "1626--1638",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

Burguillos Garcia, M, Svensson, M, Schulte, T, Boza Serrano, A, Garcia-Quintanilla, A, Kavanagh, E, Santiago, M, Viceconte, N, Oliva-Martin, MJ, Osman, AM, Salomonsson, E, Amar, L, Persson, A, Blomgren, K, Achour, A, Englund, E , Leffler, H, Venero, JL, Joseph, B & Deierborg, T 2015, 'Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.', Cell Reports, vol. 10, no. 9, pp. 1626-1638. https://doi.org/10.1016/j.celrep.2015.02.012

TY - JOUR

T1 - Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.

AU - Burguillos Garcia, Miguel

AU - Svensson, Martina

AU - Schulte, Tim

AU - Boza Serrano, Antonio

AU - Garcia-Quintanilla, Albert

AU - Kavanagh, Edel

AU - Santiago, Martiniano

AU - Viceconte, Nikenza

AU - Oliva-Martin, Maria Jose

AU - Osman, Ahmed Mohamed

AU - Salomonsson, Emma

AU - Amar, Lahouari

AU - Persson, Annette

AU - Blomgren, Klas

AU - Achour, Adnane

AU - Englund, Elisabet

AU - Leffler, Hakon

AU - Venero, Jose Luis

AU - Joseph, Bertrand

AU - Deierborg, Tomas

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041), Pathology, (Lund) (013030000), Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Neuroinflammation (013210006)

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2015.02.012

DO - 10.1016/j.celrep.2015.02.012

M3 - Article

C2 - 25753426

SN - 2211-1247

VL - 10

SP - 1626

EP - 1638

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -

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

Abstract

Bibliographical note

Subject classification (UKÄ)

Access to Document

Fingerprint

Research output

Physical exercise as a preventive strategy for disorders affecting the brain. The effect on neuroinflammation.

Microglial cells in Neurodegenerative Diseases. The Role of Galectin-3

Cite this