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Published on: March 16, 2018
Characterization of microRNA expression profiles in Leishmania-infected human phagocytes
N S Geraci1, J C Tan, M A McDowell
1Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA.
Abstract:
Leishmania are intracellular protozoa that influence host immune responses eliciting parasite species-specific pathologies. MicroRNAs (miRNAs) are short single-stranded ribonucleic acids that complement gene transcripts to block protein translation and have been shown to regulate immune system molecular mechanisms. Human monocyte-derived dendritic cells (DC) and macrophages (MP) were infected in vitro with Leishmania major or Leishmania donovani parasites. Small RNAs were isolated from total RNA and sequenced to identify mature miRNAs associated with leishmanial infections. Normalized sequence read count profiles revealed a global downregulation in miRNA expression among host cells following infection. Most identified miRNAs were expressed at higher levels in L. donovani-infected cells relative to L. major-infected cells. Pathway enrichments using in silico-predicted gene targets of differentially expressed miRNAs showed evidence of potentially universal MAP kinase signalling pathway effects. Whereas JAK-STAT and TGF-β signalling pathways were more highly enriched using targets of miRNAs upregulated in L. donovani-infected cells, these data provide evidence in support of a selective influence on host cell miRNA expression and regulation in response to differential Leishmania infections.
Insights
Leishmania parasites alter host immune cells by downregulating microRNAs (miRNAs). Differential expression of these regulatory molecules occurs between Leishmania major and Leishmania donovani infections, impacting key signaling pathways.
Area of Science:
- Immunology
- Molecular Biology
- Parasitology
Background:
- Leishmania parasites are protozoa that manipulate host immune responses, causing distinct pathologies.
- MicroRNAs (miRNAs) are crucial regulators of gene expression and immune system function.
Purpose of the Study:
- To identify host cell mature microRNAs (miRNAs) affected by Leishmania major and Leishmania donovani infections.
- To investigate the impact of differential Leishmania infections on host cell miRNA expression profiles and associated signaling pathways.
Main Methods:
- Human monocyte-derived dendritic cells (DCs) and macrophages (MPs) were infected in vitro with Leishmania major or Leishmania donovani.
- Small RNA sequencing was performed to identify and quantify mature miRNAs.
- Bioinformatic pathway enrichment analysis was used to predict the functional impact of differentially expressed miRNAs.
Main Results:
- Leishmania infection led to a global downregulation of miRNA expression in host immune cells.
- Higher levels of most identified miRNAs were observed in Leishmania donovani-infected cells compared to Leishmania major-infected cells.
- MAP kinase signaling pathways were universally affected, while JAK-STAT and TGF-β pathways were enriched in Leishmania donovani-infected cells.
Conclusions:
- Host cell miRNA expression is selectively influenced by different Leishmania species infections.
- Differential regulation of miRNAs impacts key immune signaling pathways, contributing to Leishmania-induced pathologies.
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