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Influence of L-arginine and polyamines metabolism for transcripts and microRNAs profile in murine macrophages infected with Leishmania amazonensis

Grant number: 19/07089-3
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2019
Effective date (End): September 30, 2021
Field of knowledge:Biological Sciences - Parasitology
Principal researcher:Sandra Marcia Muxel
Grantee:Jonathan Miguel Zanatta
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Mammalian host infected with protozoan parasite Leishmania amazonensis causes a cutaneous leishmaniosis, a neglected disease that present a higher prevalence in Brazil. The establishment of immunological response uses post-transcriptional resources, such as microRNAs, which are largely studied in leishmaniasis. The ways to forward the control of gene expression regulation from polyamines pathway and production of nitric oxide (NO) have been studied and guides a minucious regulatory mechanism mediated by microRNAs (miRNAs). Indeed, both parasite and macrophages use L-arginine as substrate for polyamines pathway via arginase enzyme; or NO via nitric oxide synthase; and thus modulating the balance between the survival of parasite and the establishment of inflammatory response. Thus, the combined efforts to understand the perturbation promoted by Leishmania into the host cells, evidenced the fundamental importance of the L-arginine metabolism to maintain the infection. In this way, the present proposal aims to analyze the expression of mRNAs and miRNAs involved in the L-arginine metabolism in macrophages of BALB/c mice infected with L. amazonensis, under conditions of deprivation or supplementation of L-arginine and putrescine and how these metabolites influences the infectivity, allowing or blocking parasite replication.