INVESTIGADORES
GIMENEZ Guadalupe
congresos y reuniones científicas
Título:
Enhanced Production of IL-10 in Regulatory Dendritic Cells Induced by Trypanosoma cruzi Depends on the Activation of MEK/ERK Pathway and is not Associated to TLR2 Triggering
Autor/es:
PONCINI CV,; GIMÉNEZ G,; PONTILLO C; PIAZZÓN I,; GONZÁLEZ CAPPA SM
Lugar:
Viña del Mar, Chile
Reunión:
Congreso; 9th Latin American Congress of Immunology; 2009
Resumen:
We demonstrated the ability of live trypomastigotes (Tp) to modulate differentiation stage and functionality of bone marrow-derived dendritic cells (DC) to a regulatory phenotype in vitro. Tp fail to activate DC, prevent full activation by LPS, induce high IL-10 secretion and poor alloresponse. Several groups reported T. cruzi recognition by TLRs. Here, by Western blot, we studied the activation of reported key regulators of cytokine production and DC differentiation in DC cultured with live or heat-killed Tp and/or LPS. By ELISA, we analyzed cytokine production and how it was affected by the absence of certain TLRs, using DC from TLR2 KO and TLR4-mutant mice. Live and heat-killed Tp enhanced ERK and induced STAT3 phosphorylation during LPS-stimulation. Tp enhanced IL-10 production by LPS-treated DC and MEK inhibition led to a reduced production of IL-10 (p<0.001). MEK inhibition led to a total reversion of the impaired capacity of regulatory-DC to induce a non-related antigen-specific response (p<0.01). TLR2 was not involved in the IL-10 synergism induced by Tp plus LPS as TLR4 did (p<0.01). In conclusion, Tp promoted ERK-mediated IL-10 production, heat preserved parasite-membrane structure involved in changes described and the phenomenon was independent of TLR2-ligation.