Toll-like receptor 2 ligands promote microglial cell death by inducing autophagy.
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.
Centro de Investigaciones en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Daniela S
DS
Arroyo
Javier A
JA
Soria
Emilia A
EA
Gaviglio
Constanza
C
Garcia-Keller
Liliana M
LM
Cancela
Maria C
MC
Rodriguez-Galan
Ji Ming
JM
Wang
Pablo
P
Iribarren
D000818:Animals; D001343:Autophagy; D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology*; D005434:Flow Cytometry; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D011134:Polysaccharides / Q000378:metabolism / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D008024:Ligands; D011134:Polysaccharides; D051195:Toll-Like Receptor 2