Toll-like receptor 2 ligands promote microglial cell death by inducing autophagy. FASEB J 2013 Jan;27(1):299-312
Date
10/18/2012Pubmed ID
23073832Pubmed Central ID
PMC3528320DOI
10.1096/fj.12-214312Scopus ID
2-s2.0-84871910198 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
Microglial cells are phagocytes in the central nervous system (CNS) and become activated in pathological conditions, resulting in microgliosis, manifested by increased cell numbers and inflammation in the affected regions. Thus, controlling microgliosis is important to prevent pathological damage to the brain. Here, we evaluated the contribution of Toll-like receptor 2 (TLR2) to microglial survival. We observed that activation of microglial cells with peptidoglycan (PGN) from Staphylococcus aureus and other TLR2 ligands results in cell activation followed by the induction of autophagy and autophagy-dependent cell death. In C57BL/6J mice, intracerebral injection of PGN increased the autophagy of microglial cells and reduced the microglial/macrophage cell number in brain parenchyma. Our results demonstrate a novel role of TLRs in the regulation of microglial cell activation and survival, which are important for the control of microgliosis and associated inflammatory responses in the CNS.
Author List
Arroyo DS, Soria JA, Gaviglio EA, Garcia-Keller C, Cancela LM, Rodriguez-Galan MC, Wang JM, Iribarren PAuthor
Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAutophagy
Blotting, Western
Cell Death
Flow Cytometry
Ligands
Male
Mice
Mice, Inbred C57BL
Microglia
Microscopy, Confocal
Microscopy, Electron, Transmission
Polysaccharides
Toll-Like Receptor 2