IRIBARREN PABLO
Congresos y reuniones científicas
Título:
Toll-like receptor 2 ligands promote microglial cell death by inducing autophagy
Autor/es:
IRIBARREN, P
Lugar:
Buenos Aires
Reunión:
Conferencia; Autophagy: Molecular Mechanisms in Biology and Diseases; 2013
Institución organizadora:
Facultad de Farmacia y Bioquímica de la Universidad de Buenos Aires
Resumen:

Introduction: Microglial cells (MC) 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 may prevent pathological damage to the brain. Here, we evaluated the contribution of Toll-like receptor 2 (TLR2) to microglial survival.

Material and Methods: The murine MC line BV2 and primary murine MC were stimulated with peptidoglycan (PGN) from Staphylococcus aureus at different time points. After treatment, MC were processed to evaluate: 1) cell death by flow cytometry using Annexin V Apoptosis Detection Kit; 2) autophagy activation by western blot and confocal microscopy. PGN was injected into the caudate putamen of C57BL/6J mice. Then, MC death and detection of LC3-II in MC were performed by ex vivo analysis of mice brains. All experiments were performed 3 times and p < 0.05 was considered to be statistically significant.

Results: We observed that activation of MC with PGN 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 MC and reduced the microglial/macrophage cell number in brain parenchyma.

Discussion: Our results demonstrate a novel role of TLRs in the regulation of MC activation and survival, which are important for the control of microgliosis and associated inflammatory responses in the CNS.