biostudies-literatureFernandes JCRFundação de Amparo à Pesquisa do Estado de São Paulo60https://www.ebi.ac.uk/biostudies/studies/S-EPMC6435487biostudies-literatureUnknown9Leishmaniases are neglected diseases that cause a large spectrum of clinical manifestations, from cutaneous to visceral lesions. The initial steps of the inflammatory response involve the phagocytosis of <i>Leishmania</i> and the parasite replication inside the macrophage phagolysosome. Melatonin, the darkness-signaling hormone, is involved in modulation of macrophage activation during infectious diseases, controlling the inflammatory response against parasites. In this work, we showed that exogenous melatonin treatment of BALB/c macrophages reduced <i>Leishmania amazonensis</i> infection and modulated host microRNA (miRNA) expression profile, as well as cytokine production such as IL-6, MCP-1/CCL2, and, RANTES/CCL9. The role of one of the regulated miRNA (miR-294-3p) in <i>L. amazonensis</i> BALB/c infection was confirmed with miRNA inhibition assays, which led to increased expression levels of <i>Tnf</i> and <i>Mcp-</i>1/<i>Ccl2</i> and diminished infectivity. Additionally, melatonin treatment or miR-30e-5p and miR-302d-3p inhibition increased nitric oxide synthase 2 (<i>Nos2</i>) mRNA expression levels and nitric oxide (NO) production, altering the macrophage activation state and reducing infection. Altogether, these data demonstrated the impact of melatonin treatment on the miRNA profile of BALB/c macrophage infected with <i>L. amazonensis</i> defining the infection outcome.Frontiers in cellular and infection microbiologyMelatonin and <i>Leishmania amazonensis</i> Infection Altered miR-294, miR-30e, and miR-302d Impacting on <i>Tnf</i>, <i>Mcp-1</i>, and <i>Nos</i>2 Expression.PMC64354872018/24693-92014/50717-1Aoki JIFloeter-Winter LMZampieri RAMaia Acuna SMarkus RPMuxel SMFernandes JCRfalseMelatonin and <i>Leishmania amazonensis</i> Infection Altered miR-294, miR-30e, and miR-302d Impacting on <i>Tnf</i>, <i>Mcp-1</i>, and <i>Nos</i>2 Expression.Leishmaniases are neglected diseases that cause a large spectrum of clinical manifestations, from cutaneous to visceral lesions. The initial steps of the inflammatory response involve the phagocytosis of <i>Leishmania</i> and the parasite replication inside the macrophage phagolysosome. Melatonin, the darkness-signaling hormone, is involved in modulation of macrophage activation during infectious diseases, controlling the inflammatory response against parasites. In this work, we showed that exogenous melatonin treatment of BALB/c macrophages reduced <i>Leishmania amazonensis</i> infection and modulated host microRNA (miRNA) expression profile, as well as cytokine production such as IL-6, MCP-1/CCL2, and, RANTES/CCL9. The role of one of the regulated miRNA (miR-294-3p) in <i>L. amazonensis</i> BALB/c infection was confirmed with miRNA inhibition assays, which led to increased expression levels of <i>Tnf</i> and <i>Mcp-</i>1/<i>Ccl2</i> and diminished infectivity. Additionally, melatonin treatment or miR-30e-5p and miR-302d-3p inhibition increased nitric oxide synthase 2 (<i>Nos2</i>) mRNA expression levels and nitric oxide (NO) production, altering the macrophage activation state and reducing infection. Altogether, these data demonstrated the impact of melatonin treatment on the miRNA profile of BALB/c macrophage infected with <i>L. amazonensis</i> defining the infection outcome.2019-01-01T00:00:00Z20192024-11-15T15:49:26.301Z2024-11-15T15:49:26.301ZS-EPMC64354873094945510.3389/fcimb.2019.00060