Year: 2014
Type: article
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. Methods & Materials: 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 (3 h, 6 h, 12 h and 24 h) Results: We show that expression of 64, out of 365 analyzed miRNAs, were consistently deregulated upon infection with the same trends in all donors. GO enrichment analysis of experimentally validated miRNA-targeted genes revealed that several pathways and molecular functions were disturbed upon parasite infection. Among the experimentally validated targeted transcripts of up-regulated miRNAs at 3 h, 6 h and 12 h, several belong to the chemokine family. Negative correlation between expression levels of a selected up-regulated set of miRNAs (let-7a, miR-25, miR-26a, miR-140 or miR-155 among others) and of mRNA of their corresponding chemokine targets (i.e., CCL2, CCL5, CXCL10, CXCL11 and CXCL12). Finally, following parasite infection, miR-210 abundance was enhanced in hypoxia-induced factor-1 alpha (HIF-1a)-dependent manner. Conclusion: Our data suggest that alteration in miRNA levels likely play important role in regulating macrophage functions following L. major infection. These results could contribute to better understanding the dynamics of gene expression in host cells during leishmaniasis. The two first authors contributed equally to this work and the two last authors co-directed this study.
Authors: G. Mkannez, J. Lemaire, F. Guerfali, C. Gustin, H. Attia, R.M. Sghaier, K. Dellagi, P. Renard, D. Laouini
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,900
OpenAlex ID: W4247962945