title: Essential role of leukotriene B4 on Leishmania (Viannia) braziliensis killing by human macrophages.
abstract: Although Leishmania (Viannia) braziliensis is the most prevalent species that cause American tegumentary leishmaniasis (ATL), the immune response against this parasite has been poorly investigated. Upon activation, macrophages produce a series of pro-inflammatory molecules, including the lipid mediator leukotriene B4 (LTB4). LTB4 has been shown to enhance several macrophage functions, but its role in human macrophages is less known. Here, we investigated the role of LTB4 on human monocyte-derived macrophages infected with human isolate of L. (V.) braziliensis (IMG3). It was found that human macrophages produce LTB4 upon infection with Leishmania, which by autocrine or paracrine activation of its high affinity receptor BLT1, potentiates macrophage leishmanicidal activity. This LTB4 effect is mediated by increased secretion of reactive oxygen species (ROS). Moreover, Leishmania infection decreased the expression of BLT1, leading to the speculation that this could represent a parasite escape mechanism to establish a chronic inflammatory infection. Therefore, our data suggest that LTB4 could be used in therapeutic strategies to control Leishmania infection.
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.
authors.forename: Camila I
authors.initials: CI
authors.lastname: Morato
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.
authors.forename: Ildefonso A
authors.initials: IA
authors.lastname: da Silva
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.
authors.forename: Arissa F
authors.initials: AF
authors.lastname: Borges
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Dorta
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.
authors.forename: Milton A P
authors.initials: MA
authors.lastname: Oliveira
authors.affiliation: Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jancar
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Serezani
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil. Electronic address: fatimardias@gmail.com.
authors.forename: Fátima
authors.initials: F
authors.lastname: Ribeiro-Dias
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D006801:Humans; D007892:Leishmania braziliensis / Q000276:immunology* / Q000502:physiology*; D007975:Leukotriene B4 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000469:parasitology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism*
chemical_list: C513240:LTB4R protein, human; D017382:Reactive Oxygen Species; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4
keywords: Human; LTB(4); Leishmania (V.) braziliensis; Macrophage; ROS