IRIBARREN PABLO
Congresos y reuniones científicas
Título:
AUTOPHAGY INDUCTION BY TLR2 LIGANDS REGULATES LEUKOCYTE RECRUITMENT IN THE BRAIN
Autor/es:
ARROYO, DS; GAVIGLIO, EA; PERALTA RAMOS, JM; BUSSI, C; AVALOS, P; CANCELA, LM; IRIBARREN, P
Lugar:
Mar del Plata
Reunión:
Congreso; Reunión Anual de la Sociedad Argentina de Inmunología; 2014
Institución organizadora:
SAI
Resumen:
Microglial cells (MC) are phagocytes in the central nervous
system that become activated in pathological conditions, resulting
in microgliosis, manifested by increased cell numbers and inflammation
in the affected regions. We previously demonstrated that
TLR2 has the potential to induce autophagy in MC. Considering
this, in this work we evaluated if autophagy play a role in the
regulation of the activation and the recruitment of myeloid cells to
the 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 the
number of LC3B positive CD45+ microglia/macrophages cells
in the site of injection (p<0,001). In addition, coinjection of PGN
and LY294002 or 3-MA (inhibitors of autophagy) failed to cause
the 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 in
the CD11b/CD45high fraction) in the CPU of mice compared to controls (p<0.05). We confirmed that PGN-induced recruitment of
CD11b/CD45high cells was dependent by TLR2 activation, since
injection of PGN in CPU of TLR2KO mice was unable to reproduce
that effect (p<0,001). Moreover, we found that PGN injection induced
recruitment of different CD11b/CD45high population cells to
the CPU. Therefore, we evaluated by flow citometry the phenotype
of the CD11b/CD45+ cells. We observed increased expression
of MHC class II and CD86 molecules in these cells. Finally, we
found that coinjection of PGN and LY294002 or 3M-A reduced
the recruitment of CD11b/CD45high cells to the CPU and the expression
of MHC class II and CD86 molecules in these cells. Our
results suggest that autophagy induction by TLR2 agonists may
regulate the leukocyte subpopulations in inflamed mouse brain.
system that become activated in pathological conditions, resulting
in microgliosis, manifested by increased cell numbers and inflammation
in the affected regions. We previously demonstrated that
TLR2 has the potential to induce autophagy in MC. Considering
this, in this work we evaluated if autophagy play a role in the
regulation of the activation and the recruitment of myeloid cells to
the 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 the
number of LC3B positive CD45+ microglia/macrophages cells
in the site of injection (p<0,001). In addition, coinjection of PGN
and LY294002 or 3-MA (inhibitors of autophagy) failed to cause
the 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 in
the CD11b/CD45high fraction) in the CPU of mice compared to controls (p<0.05). We confirmed that PGN-induced recruitment of
CD11b/CD45high cells was dependent by TLR2 activation, since
injection of PGN in CPU of TLR2KO mice was unable to reproduce
that effect (p<0,001). Moreover, we found that PGN injection induced
recruitment of different CD11b/CD45high population cells to
the CPU. Therefore, we evaluated by flow citometry the phenotype
of the CD11b/CD45+ cells. We observed increased expression
of MHC class II and CD86 molecules in these cells. Finally, we
found that coinjection of PGN and LY294002 or 3M-A reduced
the recruitment of CD11b/CD45high cells to the CPU and the expression
of MHC class II and CD86 molecules in these cells. Our
results suggest that autophagy induction by TLR2 agonists may
regulate the leukocyte subpopulations in inflamed mouse brain.
