Intestinal extracts of Triatoma infestans induce cell differentiation of Trypanosoma cruzi epimastigotes into the infective metacyclic form. Part of this effect can be explained by the presence of haemoglobin fragments, which stimulate trypanosomal adenylate cyclase. In this work we examined the metacyclogenic activity of lipids present in this intestinal extract. We found that lipid extracts of the intestinal extract have significant stimulatory effects that reside with the free-fatty-acid fraction, especially oleic acid. These compounds stimulate de novo diacylglycerol formation and protein kinase C activity in the parasite. Moreover, metacyclogenesis is stimulated by phorbol esters and cell-permeant diacylglycerol, while protein kinase C down-regulation or incubation with inhibitors of this kinase abrogates this effect. These results indicate that free fatty acids are a novel signal, inducing metacyclogenesis, acting through a pathway involving diacylglycerol biosynthesis and protein kinase C activation.

Here we have studied phospholipase A1 (Plase A1) from Trypanosoma cruzi infective stages and it's possible role regarding the interaction with mammalian host cells. Plase A1 was mainly detected as a membrane-bound activity in the infective amastigote and trypomastigote stages, being remarkably higher with respect to the non-infective epimastigotes. It is noteworthy that only the infective stages secreted Plase A1. Moreover, along the differentiation process from epimastigotes into metacyclic trypomastigotes, the secreted enzyme activity increased simultaneously with the appearance of metacyclic forms, as expected. Since this enzyme is predominantly membrane-associated and secreted by the infective stages, Vero cell lipid profile modifications were analysed after interaction with either intact infective parasites or purified T. cruzi Plase A1. Significant changes in Vero cell lipid composition were observed, with the appearance of free fatty acids, diacylglycerol and lysophosphatidylcholine. Concomitantly with the generation of second lipid messengers, host cell protein kinase C activation was demonstrated. These results indicate that T. cruzi Plase A1 could play a critical role in the early events of parasite-host cell interaction that precede invasion.

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