AUTOPHAGY INDUCTION BY TLR2 LIGANDS REGULATES LEUKOCYTE RECRUITMENT IN THE BRAIN

ARROYO, DS; GAVIGLIO, EA; PERALTA RAMOS, JM; BUSSI, C; AVALOS, P; CANCELA, LM; IRIBARREN, P

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Inmunología; 2014

SAI

Microglial cells (MC) are phagocytes in the central nervoussystem that become activated in pathological conditions, resultingin microgliosis, manifested by increased cell numbers and inflammationin the affected regions. We previously demonstrated thatTLR2 has the potential to induce autophagy in MC. Consideringthis, in this work we evaluated if autophagy play a role in theregulation of the activation and the recruitment of myeloid cells tothe brain. We previously observed that injection of peptidoglycan(PGN; TLR2 ligand) from S. aureus, in mouse brain parenchyma(caudate putamen; CPU), resulted in a significant increase in thenumber of LC3B positive CD45+ microglia/macrophages cellsin the site of injection (p<0,001). In addition, coinjection of PGNand LY294002 or 3-MA (inhibitors of autophagy) failed to causethe increase of LC3B punctate parenchymal microglia (p<0,001).In another set of experiments, we observed that PGN injection,increased the frecuency CD11b/CD45+ cells (and particularly inthe CD11b/CD45high fraction) in the CPU of mice compared to controls (p<0.05). We confirmed that PGN-induced recruitment ofCD11b/CD45high cells was dependent by TLR2 activation, sinceinjection of PGN in CPU of TLR2KO mice was unable to reproducethat effect (p<0,001). Moreover, we found that PGN injection inducedrecruitment of different CD11b/CD45high population cells tothe CPU. Therefore, we evaluated by flow citometry the phenotypeof the CD11b/CD45+ cells. We observed increased expressionof MHC class II and CD86 molecules in these cells. Finally, wefound that coinjection of PGN and LY294002 or 3M-A reducedthe recruitment of CD11b/CD45high cells to the CPU and the expressionof MHC class II and CD86 molecules in these cells. Ourresults suggest that autophagy induction by TLR2 agonists mayregulate the leukocyte subpopulations in inflamed mouse brain.