INVESTIGADORES
BELAUNZARAN maria Laura
congresos y reuniones científicas
Título:
Lipids from Trypanosoma cruzi amastigotes of RA and K98 strains generate a pro-inflammatory response via TLR2/6
Autor/es:
BOTT, EMANUEL; CARNEIRO, ALAN BRITO; LAMMEL, ESTELA MARÍA; BOZZA, PATRICIA T; GIMÉNEZ, GUADALUPE; BELAUNZARÁN, MARIA LAURA
Lugar:
Buenos Aires
Reunión:
Congreso; XI Congreso de la Sociedad Argentina de Protozoología, 1ra. Reunión Conjunta de Sociedades de Biociencias.; 2017
Resumen:
It is well known that lipids from microorganisms are ligands of Toll like receptors (TLRs) and are able to modulate the innate immune response. Previously we demonstrated that total lipids from Trypanosoma cruzi amastigotes of RA and K98 strains, with polar biological behavior, induced in murine macrophages lipid bodies? formation, COX-2 expression and TNF- and nitric oxide release (Bott E et al., SAP 2016).Herein, we analyze TLR involvement in T. cruzi lipid recognition and the consequent induction of pro-inflammatory parameters in HEK cells transfected with TLRs constructs (TLR2-6, TLR2-1 and TLR4) after stimulation with total lipids from RA and K98 strains (RA, K98). Besides, in order to mimic the enzymatic processes that occur during amastigote nest degeneration, where released enzymes could contribute to the generation of bioactive lipids (Wainzelbaum M et al., 2001), we also evaluated the effect of total lipids obtained from parasites incubated 16 h at 37ºC, after disruption (RAinc, K98inc). Results showed that all the lipid stimuli induced NF-B activation (Luciferase assay) and IL-8 release (ELISA) through a TLR2-6 dependent pathway and in a dose dependence manner. PPARs are a unique set of fatty acid regulated transcription factors that control lipid metabolism and inflammation. To study if PPARγ was involved in NF-κB trans-repression after T. cruzi lipid stimulation (RA, K98, RAinc, K98inc) we analyzed NF-κB activation as well as IL-8 secretion in HEK cells co-transfected with TLR2-6 and PPAR. A significant decrease in NF-κB activation and IL-8 secretion in response to T. cruzi lipids was observed, being dependent on PPAR activation.Altogether, these findings indicate a relevant role of TLR2-6 pathway in the induction of a pro-inflammatory response induced by T. cruzi lipids that could contribute to the control of infection and host survival. Our results also suggest that PPARparticipates in the regulation of this response. Supported by UBA/Conicet.