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Alterations in the composition of microRNAs in macrophages infected by Leishmania amazonensis

Grant number: 12/15263-4
Support Opportunities:Regular Research Grants
Duration: March 01, 2013 - August 31, 2015
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Sandra Marcia Muxel
Grantee:Sandra Marcia Muxel
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Lucile Maria Floeter-Winter

Abstract

The hypothesis of this project is that the miRNA profile of macrophage can be altered during entry and replication of Leishmania amazonensis infection on macrophage, and can subvert the host immune response. In this way, the change in the miRNAs profile of macrophages, it is involved in the control of pos-transcriptional levels in the intracellular signaling the pathways of the innate immunity receptors, as TLRs, in the phagolysosome maturation and activation of cytokines and iNOS (NF-kB) production, could assist the maintenance of the parasite in the endocytic vacuole, at the same time that impair the interaction with the phagolysosome, so its replication in macrophage could increase the infectivity of this parasite. In the recent years, some studies showed that the miRNAs profile of macrophages are altered during infections by bacterias e viruses, as well as cancer cells. However, it is unclear whether the infection with Leishmania can subvert the miRNAs profile of macrophages. To address this question, this Project has a main objective to assess changes in microRNAs profile of macrophages infected with L. amazonensis and its implications in the regulation of the pathways involved with phagocytosis, the permanence of the parasite in phagolysosome and its replication, as well as a decrease in response of iNOS and cytokines production. To do this, we will use L. amazonensis wild and knockout for arginase (lower infectivity), macrophages wild and knockout for MyD88 (more susceptible to infection) or treated with melatonin (phagocytic capacity) or knockdown for NF-ºB subunits, and miRNAs that have your transcript changed and that have relevance to this study will be used as "candidates" for silencing your transcription (siRNA) and analysis your impact in infectivity. (AU)

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Scientific publications
(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)
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)
MUXEL, SANDRA MARCIA; LARANJEIRA-SILVA, MARIA FERNANDA; CARVALHO-SOUSA, CLAUDIA EMANUELLE; FLOETER-WINTER, LUCILE MARIA; MARKUS, REGINA P.. The RelA/cRel nuclear factor-B (NF-B) dimer, crucial for inflammation resolution, mediates the transcription of the key enzyme in melatonin synthesis in RAW 264.7 macrophages. Journal of Pineal Research, v. 60, n. 4, p. 394-404, . (14/50717-1, 10/52688-8, 13/13691-1, 12/15263-4)
MUXEL, SANDRA MARCIA; LARANJEIRA-SILVA, MARIA FERNANDA; ZAMPIERI, RICARDO ANDRADE; FLOETER-WINTER, LUCILE MARIA. Leishmania (Leishmania) amazonensis induces macrophage miR-294 and miR-721 expression and modulates infection by targeting NOS2 and L-arginine metabolism. SCIENTIFIC REPORTS, v. 7, . (14/50717-1, 10/52688-8, 14/20809-1, 12/15263-4)

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