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The role of neutrophils as part of the innate response to <jats:italic>Leishmania<\/jats:italic> 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 <jats:italic>Leishmania<\/jats:italic> spp. are widely studied in macrophages, but scarce in neutrophils, the first cell to encounter the trypanosomatid, especially following infection by <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic>. Herein, we aimed to understand the expression patterns of coding and non-coding transcripts during acute <jats:italic>in vitro<\/jats:italic> infection of human neutrophils by <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic>. We isolated neutrophils from whole blood of healthy male donors (n = 5) and split into groups: 1) infected with <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic> (MOI = 5:1), and 2) uninfected controls. After 3 hours of exposure of infected group to promastigotes of <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic>, 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<jats:sub>2<\/jats:sub>(FC)\u00b10.58, FDR\u22640.05). <jats:italic>In vitro<\/jats:italic> infection with <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic> upregulated the expression of 197 and reduced the expression of 92 miRNAs in human neutrophils (FC\u00b12, FDR\u22640.01). 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 <jats:italic>in vitro<\/jats:italic> infection with <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic>, may impair phagocytosis, apoptosis and decrease nitric oxide production. Our work sheds light on several mechanisms used by <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic> 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.<\/jats:p>","DOI":"10.1371\/journal.pntd.0012318","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T17:30:58Z","timestamp":1721410258000},"page":"e0012318","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Leishmania infantum infection modulates messenger RNA, microRNA and long non-coding RNA expression in human neutrophils in vitro"],"prefix":"10.1371","volume":"18","author":[{"given":"Nat\u00e1lia Francisco","family":"Scaramele","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9ssica Antonini","family":"Troiano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana de Souza","family":"Felix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidnei Ferro","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Cordeiro","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1via Regina","family":"Florencio de Athayde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matheus Fujimura","family":"Soares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Fernanda da Silva","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda de Oliveira","family":"Furlan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9ria Mar\u00e7al Felix de","family":"Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-3712","authenticated-orcid":true,"given":"Flavia Lombardi","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"pntd.0012318.ref001","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrmicro2608","article-title":"Leishmaniasis: Complexity at the host-pathogen interface","volume":"9","author":"P Kaye","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"pntd.0012318.ref002","unstructured":"Pan American Health Organization. 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