Differential regulation of neuronal and microglial cell death by Toll-like receptors (TLRs)

BUSSI, C; PERALTA RAMOS, JM; GAVIGLIO, EA; ARROYO, DS; RODRIGUEZ-GALAN, MC; IRIBARREN, P

Los Cocos

Congreso; Reunion Anual de la Sociedad Argentina de Inmunología; 2013

SAI

Introduction: TLRs are a family of innate immune system receptors that respond to pathogen and damage-associated molecular patterns. TLR signaling plays an elemental role in innate and adaptative immune responses. TLRs are expressed in the central nervous system (CNS) by neurons, microglia, astrocytes, and cerebral vascular cells. Increasing evidences support the idea that TLRs are pivotal in brain pathologies such as neurodegenerative disorders. Purpose: The aim of this study was to evaluate the participation of TLRs in the regulation of neuronal and microglial cell death. Experimental procedure: Neuronal and microglial cells were stimulated with PGN (TLR2 agonist) and LPS (TLR4 agonist) at different times and doses. Cell death was evaluated using Annexin V/propidium iodide staining and subsequent flow cytometric analysis. Results: Our preliminary results show that LPS stimulation for 24 and 48 h induces a significant increase (p<0,05) in the neuronal cell death, compared to control treatment. However, PGN failed to modulate neuronal cell death. On the other hand, the stimulation of TLR2 with PGN caused significant cell death (p<0,05) of microglial cells after 48hrs of treatment, but LPS could not affect microglial cell survival. In addition, previous results from our research group demonstrated that TLR2 ligands promote neuroinflammation and microglial cell death by inducing autophagy. Therefore, we are currently evaluating if the activation of autophagy or pro-inflamatory mediators are able to regulate microglial and neuronal cell survival. Conclusion: Neuronal and microglial cell viability was affected after treatment with LPS and PGN, respectively. Our results suggest a differential involvement of different TLRs family members in the modulation of neuronal and microglial cell survival.