CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Myeloid supresor cells as possible natural regulador of inflammation in experimental Trypanosoma cruzi infection.
Autor/es:
AROCENA A, PAROLI A, PELLEGRINI A, ONOFRIO L, CANO R, CARRERA EA, AOKI P, GEA S.
Lugar:
Bs As
Reunión:
Congreso; First French-Argentine Immunology Congress (FAIC) and LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010
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.