Myeloid suppressor cells as possible natural regulator of inflammation in experimental Trypanosoma cruzi infection

AROCENA, ALFREDO ; PAROLI, AUGUSTO; PELLEGRINI, ANDREA; ONOFRIO, LUISINA; CANO, ROXANA; CARRERA, ANTONIO; AOKI, PILAR; GEA, SUSANA

Buenos Aires

Congreso; First Franco-Argentine Immunology Congress: FAIC 2010; 2010

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