CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Myeloid suppressor cells as possible natural regulator of inflammation in experimental Trypanosoma cruzi infection
Autor/es:
AROCENA A; PELLEGRINI A; PAROLI A; ONOFRIO L; CANO R.C.; AOKI MP; GEA S
Lugar:
Buenos Aires
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Institución organizadora:
Sociedad Argentina de Inmunologia
Resumen:
Myeloid-derived suppressor cells (MDSCs) accumulate during cancer and
infection and have the ability to suppress T-cell response. Their surface markers are CD11b+ Gr1+ and the
suppressor mechanisms include production of reactive oxygen species (ROS), the
induction of nitric oxide (NO) and/or arginase-1 (Arg-1) expression. Our group
previously demonstrated that infection with 1000 trypomastigotes Tulahuen
produced a significant increase in hepatic and spleen MDSC of BALB/c vs C57BL/6
(B6) mice. A strong pro-inflammatory profile and severe hepatic damage were
observed in B6. Purified MDSC significantly decreased cell proliferation
induced by ConA. To gain insight into the MDSC mechanisms, we investigated the
production of NO by splenocytes stimulated with TLRs ligands, and purified MDSC
from infected BALB/c to analyze the presence of Arg-1. Furthermore, we
quantified TLR2 and 4 mRNA in hepatic tissue of infected BALB/c and C57BL/6
mice by RT-qPCR. The NO concentration (by Griess) significantly increased when
Pam3Csk4 (TLR2 ligand) or LPS (TLR4 ligand) were added to BALB/c cells
(p<0,001). The NO produced by MDSC revealed a greater number of fluorescent
DAF-2DA positive cells in infected vs uninfected mice (p<0,05). In addition,
the presence of Arg-1 was detected in purified MDSC from BALB/c by WB, while it
was absent in uninfected mice. The study of TLR2 and 4 mRNA comparing infected
vs uninfected mice showed an upregulation of TLR2 at 14 and 21 dpi in BALB/c
mice (P<0.001), whereas a slight increase of
TLR2 was observed in B6 at 14 dpi(p<0,001) and no change at 21 dpi.
TLR4 showed a TLR2 similar kinetic at 14 and at 21 dpi in BALB/c (p<0,05 and
p<0,01 respectively). On the contrary, in B6, TLR4 was downregulated at all
times assayed. These results suggest that the MDSC present in infected BALB/c
could exert suppression through NO and Arg-1 production. The different
modulation of TLR2 and TLR4 mRNA in liver associated with a greater number of
MDSC in BALB/c would regulate the hepatic injury in this strain