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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Leishmania (Leishmania) amazonensis induces macrophage miR-294 and miR-721 expression and modulates infection by targeting NOS2 and L-arginine metabolism

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Author(s):
Muxel, Sandra Marcia ; Laranjeira-Silva, Maria Fernanda ; Zampieri, Ricardo Andrade ; Floeter-Winter, Lucile Maria
Total Authors: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, MAR 9 2017.
Web of Science Citations: 26
Abstract

Leishmania (Leishmania) amazonensis is an intracellular protozoan parasite responsible for the cutaneous leishmaniasis. The parasite replicates inside mammalian macrophage to establish infection. Host-pathogen interactions result in microRNA-mediated post-transcriptional regulation of host genes involved in inflammatory immune response. We analyzed macrophage miRNA profiles during L. (L.) amazonensis infection. The regulation of macrophage miRNA expression by the parasite correlates with/depends on parasite arginase activity during infection. L. (L.) amazonensis (La-WT) presented significant miRNA profile alteration (27%) compared to L. (L.) amazonensis arginase knockout (La-arg(-)) (similar to 40%) in relation to uninfected-macrophages. We observed that 78% of the altered miRNAs were up-regulated in La-WT infection, while only 32% were up-regulated in La-arg(-)-infected macrophages. In contrast to La-WT, the lack of L. (L.) amazonensis arginase led to the inhibition of miR-294 and miR721 expression. The expression of miR-294 and miR-721 was recovered to levels similar to La-WT in La-arg(-)addback mutant. The inhibition of miR-294/Nos2 and miR721/Nos2 interactions increased NOS2 expression and NO production, and reduced L. (L.) amazonensis infectivity, confirming Nos2 as target of these miRNAs. The role of miR-294 and miR-721 in the regulation of NOS2 expression during Leishmania replication in infected macrophages pointing these miRNAs as potential new targets for drug development. (AU)

FAPESP's process: 10/52688-8 - Biochemical, physiological and functional genomics studies of Leishmania-macrophage interaction
Grantee:Lucile Maria Floeter-Winter
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/15263-4 - Alterations in the composition of microRNAs in macrophages infected by Leishmania amazonensis
Grantee:Sandra Marcia Muxel
Support type: Regular Research Grants
FAPESP's process: 14/50717-1 - Biochemical, physiological and functional genomic studies of Leishmania-macrophage interaction
Grantee:Lucile Maria Floeter-Winter
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/20809-1 - Multiuser equipment approved in grant 2013/13691-1 - for acquisition of AMNIS flow-sight - Millipore
Grantee:Regina Pekelmann Markus
Support type: Multi-user Equipment Program