Leishmania is a protozoan parasite that alternates its life cycle between the sand fly and the mammalian hosts. This alternation involves environmental changes and submits the parasite to dynamic modifications in morphology, metabolism, cellular signaling and gene expression regulation to allow a rapid adaptation to new conditions. Our research group have been studying the role of arginase in L. amazonensis during the parasite life cycle and its role in the establishment and maintenance of the infection in mammalian macrophages. Arginase is an immune-regulatory enzyme, which can reduce the nitric oxide concentrations produced by activated macrophages and limit the availability of L-arginine, regulating the polyamines pathway, supporting the resistance of some pathogens to host defense mechanisms. Currently, we described by RNA-seq technology, the differential gene expression profile on polyamines pathway in promastigotes and axenic amastigotes regulated by arginase activity. Our goal in this project is to identify gene signature and differential gene expression profile between two mice strains, one highly susceptible and another less susceptible to L. amazonensis (La-WT) or L. amazonensis arginase knockout (La-arg-) infections. Further, validate and correlate the miRNAs participation that has been providing interesting data on understanding how regulation of gene expression is used by Leishmania to subvert the macrophage defenses.
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