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MicroRNA expression profile in human macrophages in response to Leishmania major infection
Julien Lemaire1, Ghada Mkannez, Fatma Z Guerfali
1Laboratory of Biochemistry and Cellular Biology (URBC), NARILIS-University of Namur, Namur, Belgium.
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.
Insights
Leishmania major infection alters microRNA (miRNA) expression in macrophages, impacting host cell functions. Understanding these miRNA changes is key to leishmaniasis pathogenesis.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Leishmania parasites infect macrophages, causing leishmaniasis, a neglected tropical disease.
- Leishmania employs sophisticated strategies to evade host immune responses within macrophages.
- MicroRNAs (miRNAs) are key regulators of gene expression, influencing cellular processes.
Purpose of the Study:
- To comprehensively analyze miRNA expression profiles in Leishmania major-infected human macrophages.
- To identify specific miRNAs and pathways affected by L. major infection.
- To elucidate the role of miRNAs in host-parasite interactions.
Main Methods:
- Analysis of miRNA expression profiles in human primary macrophages from healthy donors at various time points post-infection.
- Identification of deregulated miRNAs using bioinformatics.
- Gene Ontology (GO) enrichment analysis of miRNA-targeted genes.
- Assessment of miR-210 and HIF-1α pathway involvement.
Main Results:
- Consistent deregulation of 64 out of 365 analyzed miRNAs in L. major-infected macrophages across all donors.
- Identification of several miRNAs induced by Toll-like receptor (TLR)-dependent responses.
- Disturbance of multiple cellular pathways and molecular functions due to parasite infection.
- Enhanced abundance of miR-210 in a HIF-1α-dependent manner, without affecting caspase-3 regulation.
Conclusions:
- Altered miRNA levels significantly regulate macrophage functions during L. major infection.
- These findings enhance understanding of host gene expression dynamics in leishmaniasis.
- miRNA profiling offers insights into host-pathogen interactions and potential therapeutic targets.
