Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPFERNANDES, Juliane Cristina RibeiroAOKI, Juliana IdeACUNA, Stephanie MaiaZAMPIERI, Ricardo AndradeMARKUS, Regina P.FLOETER-WINTER, Lucile MariaMUXEL, Sandra Marcia2019-05-302019-05-302019FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v.9, article ID 60, 15p, 20192235-2988https://observatorio.fm.usp.br/handle/OPI/32030Leishmaniases 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 Leishmania 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 Leishmania amazonensis 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 L. amazonensis BALB/c infection was confirmed with miRNA inhibition assays, which led to increased expression levels of Tnf and Mcp-1/Ccl2 and diminished infectivity. Additionally, melatonin treatment or miR-30e-5p and miR-302d-3p inhibition increased nitric oxide synthase 2 (Nos2) 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 L. amazonensis defining the infection outcome.engopenAccesspolyamine pathwaynitric oxide synthasearginase 1interleukinmRNA-miRNA interactionmelatonin and Leishmanianitric-oxide synthasegene-expressionmice lackingmacrophage activationmurine macrophagesimmune-responsesstromal cellsmicrornasinductionsurvivalarticleCopyright FRONTIERS MEDIA SA10.3389/fcimb.2019.00060ImmunologyMicrobiology