Leishmania infantum infection modulates messenger RNA, microRNA and long non-coding RNA expression in human neutrophils in vitro

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 lon...

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Published in:PLoS neglected tropical diseases 2024-07, Vol.18 (7), p.e0012318
Main Authors: Scaramele, Natália Francisco, Troiano, Jéssica Antonini, Felix, Juliana de Souza, Costa, Sidnei Ferro, Almeida, Mariana Cordeiro, Florencio de Athayde, Flávia Regina, Soares, Matheus Fujimura, Lopes, Maria Fernanda da Silva, Furlan, Amanda de Oliveira, Lima, Valéria Marçal Felix de, Lopes, Flavia Lombardi
Format: Article
Language:English
Subjects:
Genetic aspects
Health aspects
Immune response
Leishmania
Leishmaniasis
Medical research
Medicine, Experimental
Neutrophils
Physiological aspects
RNA
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Summary: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 (log.sub.2 (FC)±0.58, FDR[less than or equal to]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[less than or equal to]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.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0012318