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Published on: March 16, 2018
Leishmania infantum infection modulates messenger RNA, microRNA and long non-coding RNA expression in human
Natália Francisco Scaramele1, Jéssica Antonini Troiano1, Juliana de Souza Felix1
1Department of Production and Animal Health, São Paulo State University (Unesp), School of Veterinary Medicine, Araçatuba, São Paulo, Brazil.
Abstract:
In the Americas, L. infantum (syn. chagasi) is the main cause of human visceral leishmaniasis. The role of neutrophils as part of the innate response to Leishmania spp. infection is dubious and varies according to the species causing the infection. Global expression of coding RNAs, microRNAs and long non-coding RNAs changes as part of the immune response against pathogens. Changes in mRNA and non-coding RNA expression resulting from infection by Leishmania spp. are widely studied in macrophages, but scarce in neutrophils, the first cell to encounter the trypanosomatid, especially following infection by L. infantum. Herein, we aimed to understand the expression patterns of coding and non-coding transcripts during acute in vitro infection of human neutrophils by L. infantum. We isolated neutrophils from whole blood of healthy male donors (n = 5) and split into groups: 1) infected with L. infantum (MOI = 5:1), and 2) uninfected controls. After 3 hours of exposure of infected group to promastigotes of L. infantum, followed by 17 hours of incubation, total RNA was extracted and total RNA-Seq and miRNA microarray were performed. A total of 212 genes were differentially expressed in neutrophils following RNA-Seq analysis (log2(FC)±0.58, FDR≤0.05). In vitro infection with L. infantum upregulated the expression of 197 and reduced the expression of 92 miRNAs in human neutrophils (FC±2, FDR≤0.01). Lastly, 5 downregulated genes were classified as lncRNA, and of the 10 upregulated genes, there was only 1 lncRNA. Further bioinformatic analysis indicated that changes in the transcriptome and microtranscriptome of neutrophils, following in vitro infection with L. infantum, may impair phagocytosis, apoptosis and decrease nitric oxide production. Our work sheds light on several mechanisms used by L. infantum to control neutrophil-mediated immune response and identifies several targets for future functional studies, aiming at the development of preventive or curative treatments for this prevalent zoonosis.
Insights
This study reveals how Leishmania infantum infection alters gene and microRNA expression in human neutrophils. These changes may impair neutrophil functions like phagocytosis and apoptosis, aiding parasite survival.
Area of Science:
- Immunology
- Molecular Biology
- Parasitology
Background:
- Visceral leishmaniasis, caused by Leishmania infantum, is a significant public health concern in the Americas.
- The role of neutrophils in Leishmania spp. infection immunity is not fully understood, with limited research on their transcriptomic response, especially to L. infantum.
- Neutrophils are the first immune cells to encounter Leishmania parasites during infection.
Purpose of the Study:
- To investigate the expression patterns of coding and non-coding RNA transcripts in human neutrophils during acute in vitro infection with Leishmania infantum.
- To elucidate the molecular mechanisms by which L. infantum influences neutrophil behavior and immune response.
Main Methods:
- Human neutrophils were isolated from healthy donors and infected in vitro with L. infantum (MOI = 5:1).
- Total RNA was extracted after 3 hours of infection followed by 17 hours of incubation.
- Total RNA-Seq and miRNA microarray analyses were performed to assess gene and microRNA expression changes.
Main Results:
- RNA-Seq analysis revealed 212 differentially expressed genes in neutrophils post-infection.
- Microarray analysis showed 197 upregulated and 92 downregulated microRNAs in human neutrophils.
- Bioinformatic analysis suggested that observed transcriptomic and microtranscriptomic changes may impair neutrophil phagocytosis, apoptosis, and nitric oxide production.
Conclusions:
- Leishmania infantum significantly alters the expression of coding and non-coding RNAs in human neutrophils during early infection.
- These molecular changes likely contribute to L. infantum's ability to evade or manipulate neutrophil-mediated immune responses.
- The study identifies potential molecular targets for developing novel preventive or curative strategies against this zoonotic disease.
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