Lipids from Leishmania amazonensis and Leishmania braziliensis promastigotes promote macrophage polarization

LÓPEZ, SEBASTIÁN; PENAS, FEDERICO; LAUTHIER JUAN JOSÉ; CADENA, MARÍA FERNANDA; GOREN, NORA; RUYBAL, PAULA; GIMENEZ, GUADALUPE; BELAUNZARÁN, MARÍA LAURA

Sao Paulo

Encuentro; II Host-Pathogen Interaction Meeting 2022; 2022

INTRODUCTION: Macrophages (Mo) can be activated via classical (M1) and alternative (M2) activation. Control of Leishmania spp. infection requires a Th1 response & M1Mo activation. However, Th2 response and M2Mo activation can lead to parasite establishment in the host cell.OBJECTIVES: This work analyzes the biological effects of L.amazonensis (Lama) and L.braziliensis (Lbra) lipids from lysed promastigotes in murine peritoneal Mo activation.METHODS:L.braziliensis M2904 & L.amazonensis PH8 promastigotes strains were axenically cultured in supplemented RPMI medium at 24ºC. Peritoneal Mo were obtained from BALB/c mice. Briefly, parasites were disrupted, total lipids were extracted according to Bligh & Dyer and suspended in ethanol for Mo stimulation. Lipid bodies (LB), Nitric Oxide (NO), Arginase activity (Aa) & M1/M2 markers mRNA were determined as described (Bott et al., 2018; Penas et al., 2017).RESULTS: Lama & Lbra induced a significant number of LB, with respect to control (~10.7 & 10.3 vs 4.5 LB/Mo). In relation to inducible nitric oxide synthase (iNOS) activity, associated with M1Mo activation, Lama induced significant NO release (32.3 µM), as determined by the Griess reaction. However, Lbra (14µM) showed no significant differences in NO release when compared to control (10.4 µM). Moreover, Lama & Lbra induced significant Aa, M2Mo marker, with respect to control. Lbra induced the highest values of Aa followed by Lama (~14 & 7.5 vs 1.7 μg urea/μg protein/h). Finally, we determined by RT–qPCR that Lama induced higher levels of TNFα mRNA expression (M1Mo marker) than Lbra. In contrast, Lbra induced a significant level of IL-10 mRNA expression, but Lama showed no significant differences with respect to control. As regards other M2Mo markers, we observed that Lbra & Lama induced significant levels of FIZZ1 mRNA expression (~20.3 & 24 times vs control) and in the case of YM1 mRNA expression both Lbra & Lama showed significant levels (~4.8 & 7.9 times vs. control).CONCLUSION: L.amazonensis and L.braziliensis promastigotes possess bioactive lipids which can modulate macrophages responses and might contribute for parasite control/ survival. Granted by UBA/CONICET/FONCyT