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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 Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2018
Effective date (End): January 31, 2023
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Sandra Marcia Muxel
Grantee:Stephanie Maia Acuna
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):21/07144-4 - Immunometabolic networks during dendritic cell-Leishmania interactions, BE.EP.DD


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)

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Scientific publications (9)
(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)
ZANATTA, JONATHAN MIGUEL; ACUNA, STEPHANIE MAIA; ANGELO, YAN DE SOUZA; BENTO, CAMILLA DE ALMEIDA; PERON, JEAN PIERRE SCHATZMAN; STOLF, BEATRIZ SIMONSEN; MUXEL, SANDRA MARCIA. Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection. PLoS One, v. 18, n. 3, p. 25-pg., . (17/23519-2, 22/00291-4, 18/24693-9, 18/18499-5, 19/07089-3)
ACUNA, STEPHANIE MAIA; ZANATTA, JONATHAN MIGUEL; DE ALMEIDA BENTO, CAMILLA; FLOETER-WINTER, LUCILE MARIA; MUXEL, SANDRA MARCIA. iR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensi. ON-CODING RN, v. 8, n. 1, . (18/24693-9, 19/07089-3, 18/18499-5, 17/23519-2, 14/50717-1)
ACUNA, STEPHANIE MAIA; FLOETER-WINTER, LUCILE MARIA; MUXEL, SANDRA MARCIA. MicroRNAs: Biological Regulators in Pathogen-Host Interactions. CELLS, v. 9, n. 1, . (17/23519-2, 18/23512-0, 18/24693-9)
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, . (16/03273-6, 17/23519-2, 14/20809-1, 14/50717-1, 16/19815-2)
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, . (17/23519-2, 18/23512-0, 18/24693-9, 16/03273-6)
MAMANI-HUANCA, MARICRUZ; MUXEL, SANDRA MARCIA; ACUNA, STEPHANIE MAIA; FLOETER-WINTER, LUCILE MARIA; BARBAS, CORAL; LOPEZ-GONZALVEZ, ANGELES. Metabolomic Reprogramming of C57BL/6-Macrophages during Early Infection with L. amazonensis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 13, . (17/23519-2, 18/24693-9, 18/23512-0)
CUNHA, MARIELTON DOS PASSOS; VILELA, ANA PAULA PESSOA; MOLINA, CAMILA VIEIRA; ACUNA, STEPHANIE MAIA; MUXEL, SANDRA MARCIA; BARROSO, VINICIUS DE MORAIS; BARONI, SABRINA; GOMES DE OLIVEIRA, LILIAN; ANGELO, YAN DE SOUZA; PERON, JEAN PIERRE SCHATZMANN; et al. Atypical Prolonged Viral Shedding With Intra-Host SARS-CoV-2 Evolution in a Mildly Affected Symptomatic Patient. FRONTIERS IN MEDICINE, v. 8, . (19/20708-4, 18/11612-0, 17/27131-9, 19/24518-5, 17/23519-2, 20/01487-4)
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, . (16/19815-2, 16/03273-6, 12/15263-4, 14/50717-1, 17/23519-2)
FERNANDES, JULIANE C. R.; ACUNA, STEPHANIE M.; AOKI, JULIANA, I; FLOETER-WINTER, LUCILE M.; MUXEL, SANDRA M.. Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease. NON-CODING RNA, v. 5, n. 1, p. 25-pg., . (17/23519-2, 14/50717-1, 16/03273-6, 16/19815-2, 18/24693-9, 17/21906-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ACUNA, Stephanie Maia. MicroRNAs and immunometabolism of macrophages and dendritic cells during the response against Leishmania spp. genus parasites.. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.

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