CONICET | Buscador de Institutos y Recursos Humanos

Modulation of innate immunity by Autophagy: the impact on neuroiflammation and leukemia cell biologyPablo IribarrenE-mail: piribarr@fcq.unc.edu.arCIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Autophagy plays a crucial role in neurodegenerative diseases, although the precise mechanisms underlying these processes are poorly understood and little is known about the effects of the autophagic process and its regulation in microglial cells (MC). In addition, autophagy has dual role in cancer depending of the type of tumor and this response can promote cell survival or cell death, as well. Our laboratory was focused in studying the role of autophagy in the regulation of neuroinflammation and leukemia cell biology. We evaluated the effects of autophagy on the production of pro-inflammatory mediators by alpha-synuclein (α-syn)-stimulated MC, and on neuronal viability in a co-culture system. In addition, we studied the autophagy dynamics in MC after α-syn stimulation. We found that autophagy induction in MC before exogenous α-syn stimulation, downregulated IL1β, IL-6, TNF-α and NO production.Furthermore, we showed by time-lapse experiments with BV2 GFP-LC3 microglial cells that LC3B is attracted by lysosomes containing α-syn fibrils and we demonstrated by live-CLEM imaging that α-syn is targeted by autophagic vesicles. On the other hand, autophagy inhibition led to α-syn-stimulated MC death, indicating a protective role for autophagy during this process.In another set of experiments we observed that stimulation of TLR2 in MC induced cell activation, autophagy and autophagy-dependent cell death in vitro and in vivo. Now, preliminary results indicate that TLR2 stimulation in Chronic Lymphocytic Leukemia (CLL) cells induces increased levels of LC3B II and modulated Fludarabine-induced apoptosis. Overall, our results suggest that autophagy may play a role in the modulation of neuroinflammation and leukemia cell death.