Investigation of miR-294 and miR-302 regulation of response in macrophages infected with L. infantum

• Grant number: 24/06756-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2024
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Sandra Marcia Muxel
• Grantee: Victória de Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In this project, we aim to investigate their influence on the regulation of the expression of miR-294 and miR-302 during the response of macrophages infected with L. infantum. We formulated the hypothesis that infection with L. infantum increases the expression of miR-294 and miR-302 and these affect the mRNA levels of target genes related to the production of cytokines and NO in macrophages. The network of signals mediated by these molecules alters macrophage activation, increasing susceptibility to infection. MiRNAs are small non-coding RNAs that regulate gene expression by pairing their seed (6-9 nt) with the complementary 3'UTR sequence of the target mRNA, promoting degradation or inhibition of mRNA translation. The miR-294 and miR-302 acts regulating the Tnf and Nos2 mRNA genes, reducing NO production and increasing infection with L. amazonensis. Therefore, it is important to understand the correlation between parasite survival and the expression of miRNAs and their target genes in macrophages infected by L. infantum, which causes visceral leishmaniasis, and how the modulation of these molecules impacts the activation of the pro-inflammatory response and subversion of the host's response to the parasite.