INVESTIGADORES
IRIBARREN Pablo
congresos y reuniones científicas
Título:
Autophagy induction by TLR2 ligands regulate neuroinflammatory response
Autor/es:
ARROYO, DS; GAVIGLIO, EA; PERALTA RAMOS, JM; BUSSI, C; GARCIA-KELLER, C; CANCELA, LM; RODRIGUEZ-GALAN, MC; IRIBARREN, P
Lugar:
Los Cocos
Reunión:
Congreso; Reunion Anual de la Sociedad Argentina de Inmunología; 2013
Resumen:
Microglial
cells (MC) are phagocytes in the central nervous system (CNS) that 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. We
previously observed that activation of MC with peptidoglycan (PGN) from S. aureus
and another synthetic Toll-like receptor 2 (TLR2) ligand (Pam3CSK4) results in
the induction of autophagy. Due to the potential of TLR2 to act as up-regulator
of autophagy in MC, here, we examined if the activation of this receptor can
regulate the production of pro-inflammatory molecules in brain MC by inducing
autophagy. We observed that PGN or
Pam3CSK4 induced nitric oxide production in MC, was significantly reduced in the
presence of autophagy inhibitors (3-MA or LY294002)(p<0,05). Moreover, we
found that IL1beta production in MC cells stimulated with PGN or
Pam3CSK4 was reduced in the presence of both inhibitors (p<0,05). However,
the TLR2-induced production of TNFalfa was not affected by the inhibition of autophagy.
In
another set of experiments, we evaluated the frecuency of myeloid cells in the
mouse brain parenchyma (CPU) after intracerebral injection of PGN. We observed, by flow cytometry, an increase
in the frecuency CD11b/CD45+ cells (and particularly in the CD11b/CD45high
fraction) in the CPU of mice injected with PGN compared to controls
(p<0.05). In addition, we observed, by confocal microscopy, increased number
of CD45high cells around of site injection. Currently, we are
evaluating if the autophagy response play a role in the regulation of the
activation and the recruitment of myeloid cells to the brain. Our results
suggest that autophagy induction by TLR2 agonists may selectively regulate the
production of pro-inflammatory molecules by MC.