Analysis of the function of long noncoding factor regulatory RNAs NFkB transcription in macrophages infected with L. infantum.

• Grant number: 24/06780-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2024
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Sandra Marcia Muxel
• Grantee: Carlos Neandro Cordeiro Lima
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In this project, we aim to evaluate the function of the long non-coding (lncRNAs) NKILA and PACER in the regulation of NF-kB and activation of microbicidal mechanisms in macrophages infected with Leishmania infantum. We formulated the hypothesis that infection with L. infantum alters the expression of the lncRNAs NKILA and PACER and consequently the activation of NFkB and genes for the activation of macrophage microbicidal mechanisms. Infection with Leishmania alters the expression of lncRNAS and also the activation of NF-kB and consequently the activation of the pro-inflammatory response of macrophages in response to the parasite. The interaction between lncRNAs NKILA and the IºB± protein negatively regulates NF-kB, while PACER interacts with the NF-kB p50/p50 dimer and positively regulates the induction of cytokine gene expression and nitric oxide production, which can lead to susceptibility to infection. Our initial data suggest that infection with L. infantum regulates the expression of NKILA and PACER differently to LPS stimulation in THP-1 macrophages. Understanding the modulation of macrophage activation mediated by NKILA-IºB± and PACER-p50/p50, their influence on the transcriptional regulation of genes related to resistance to infection is extremely relevant to understand how parasite and host factors contribute to the pathogenesis of leishmaniasis.