Analysis of role of miRNAs and transcription factors on the regulation of gene expression of Leishmania amazonensis infected murine macrophages

• Grant number: 17/23519-2
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): March 01, 2018
• Effective date (End): January 31, 2022
• Field of knowledge: Biological Sciences - Parasitology
• Principal researcher: Sandra Marcia Muxel
• Grantee: Stephanie Maia Acuna
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leishmania is a protozoan parasite that is the causative agent of Leishmaniasis. This parasite alternate its life cycle between promastigotes inside the invertebrate host and amastigotes inhabiting immune phagocytic cells on the vertebrate host, among then, the macrophages. Parasites subvert the activation of macrophages microbicidal mechanisms, favoring the polyamines production by the Arginase (ARG1) activity in detriment of Nitric Oxide (NO) production by Nitric Oxide Synthase 2 (NOS2); both enzymes use L-arginine as a substrate. The immune response against intracellular pathogens is orchestrated by many regulatory mechanisms that operate at transcriptional or post-transcriptional levels, such as transcription factors, mRNA stabilization or miRNAs. Transcription factors are proteins that bind on target genes' promoter region allowing or repressing transcription. On the other hand, miRNAs are small non-coding RNAs that bind on the 3' UTR portion of target mRNAs, inhibiting its translation.Therefore, the infection with L. amazonensis can induce the expression of both transcription factors and miRNAs that would modulate gene expression. In addition, interaction between both mechanisms can favor the parasite elimination or allow its survival, depending on the pathway that is activated. This work aims to stablish miRNAs and transcription factors profile expression during C57BL/6 murine macrophages infection with L. amazonensis and analyze the interplay between these modulators, as well as their actions on the mounting of inflammatory response. This work also aims to evaluate the role of host NOS2 and the parasite's arginase activities and their contribution to the immune response. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ACUNA, STEPHANIE MAIA; FLOETER-WINTER, LUCILE MARIA; MUXEL, SANDRA MARCIA. MicroRNAs: Biological Regulators in Pathogen-Host Interactions. CELLS, v. 9, n. 1 JAN 2020. Web of Science Citations: 0.

MARCIA MUXEL, SANDRA; MAMANI-HUANCA, MARICRUZ; AOKI, JULIANA IDE; ZAMPIERI, RICARDO ANDRADE; FLOETER-WINTER, LUCILE MARIA; LOPEZ-GONZALVEZ, ANGELES; BARBAS, CORAL. Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 24 DEC 2019. Web of Science Citations: 0.

RIBEIRO FERNANDES, JULIANE CRISTINA; AOKI, JULIANA IDE; ACUNA, STEPHANIE MAIA; ZAMPIERI, RICARDO ANDRADE; MARKUS, REGINA P.; FLOETER-WINTER, LUCILE MARIA; MUXEL, SANDRA MARCIA. Melatonin and Leishmania amazonensis Infection Altered miR-294, miR-30e, and miR-302d Impacting on Tnf, Mcp-1, and Nos2 Expression. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 9, MAR 20 2019. Web of Science Citations: 2.

MUXEL, SANDRA MARCIA; ACUNA, STEPHANIE MAIA; AOKI, JULIANA IDE; ZAMPIERI, RICARDO ANDRADE; FLOETER-WINTER, LUCILE MARIA. Toll-Like Receptor and miRNA-let-7e Expression Alter the Inflammatory Response in Leishmania amazonensis-Infected Macrophages. FRONTIERS IN IMMUNOLOGY, v. 9, NOV 29 2018. Web of Science Citations: 3.