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  MicroRNA expression profile in human macrophages in response to Leishmania major infection

Lemaire, J., Mkannez, G., Guerfali, F. Z., Gustin, C., Attia, H., Sghaier, R. M., et al. (2013). MicroRNA expression profile in human macrophages in response to Leishmania major infection. PLoS Neglected Tropical Diseases, 7(10): e2478. doi:10.1371/journal.pntd.0002478.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-0210-A Version Permalink: http://hdl.handle.net/21.11116/0000-0001-0211-9
Genre: Journal Article

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© 2013 Lemaire et al

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 Creators:
Lemaire, Julien , Author
Mkannez, Ghada , Author
Guerfali, Fatma Z. , Author
Gustin, Cindy , Author
Attia, Hanène, Author
Sghaier, Rabiaa M. , Author
Sysco-Consortium, Author
Herwig, Ralf1, Author              
Dellagi, Koussay , Author
Laouini, Dhafer , Author
Renard, Patricia , Author
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              

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 Abstract: BACKGROUND: Leishmania (L.) are intracellular protozoan parasites able to survive and replicate in the hostile phagolysosomal environment of infected macrophages. They cause leishmaniasis, a heterogeneous group of worldwide-distributed affections, representing a paradigm of neglected diseases that are mainly embedded in impoverished populations. To establish successful infection and ensure their own survival, Leishmania have developed sophisticated strategies to subvert the host macrophage responses. Despite a wealth of gained crucial information, these strategies still remain poorly understood. MicroRNAs (miRNAs), an evolutionarily conserved class of endogenous 22-nucleotide non-coding RNAs, are described to participate in the regulation of almost every cellular process investigated so far. They regulate the expression of target genes both at the levels of mRNA stability and translation; changes in their expression have a profound effect on their target transcripts. METHODOLOGY/PRINCIPAL FINDINGS: We report in this study a comprehensive analysis of miRNA expression profiles in L. major-infected human primary macrophages of three healthy donors assessed at different time-points post-infection (three to 24 h). We show that expression of 64 out of 365 analyzed miRNAs was consistently deregulated upon infection with the same trends in all donors. Among these, several are known to be induced by TLR-dependent responses. GO enrichment analysis of experimentally validated miRNA-targeted genes revealed that several pathways and molecular functions were disturbed upon parasite infection. Finally, following parasite infection, miR-210 abundance was enhanced in HIF-1α-dependent manner, though it did not contribute to inhibiting anti-apoptotic pathways through pro-apoptotic caspase-3 regulation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that alteration in miRNA levels likely plays an important role in regulating macrophage functions following L. major infection. These results could contribute to better understanding of the dynamics of gene expression in host cells during leishmaniasis.

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Language(s): eng - English
 Dates: 2013-10-03
 Publication Status: Published online
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 Identifiers: DOI: 10.1371/journal.pntd.0002478
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Title: PLoS Neglected Tropical Diseases
Source Genre: Journal
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Publ. Info: San Francisco, CA : PLoS
Pages: - Volume / Issue: 7 (10) Sequence Number: e2478 Start / End Page: - Identifier: ISSN: 1935-2727 (print) 1935-2735 (electronic)