title: Understanding the mechanisms controlling Leishmania amazonensis infection in vitro: the role of LTB4 derived from human neutrophils.
abstract: Neutrophils are rapidly recruited to the site of Leishmania infection and play an active role in capturing and killing parasites. They are the main source of leukotriene B4 (LTB4), a potent proinflammatory lipid mediator. However, the role of LTB4 in neutrophil infection by Leishmania amazonensis is not clear. In this study, we show that L. amazonensis or its lipophosphoglycan can induce neutrophil activation, degranulation, and LTB4 production. Using pharmacological inhibitors of leukotriene synthesis, our findings reveal an LTB4-driven autocrine/paracrine regulatory effect. In particular, neutrophil-derived LTB4 controls L. amazonensis killing, degranulation, and reactive oxygen species production. In addition, L. amazonensis infection induces an early increase in Toll-like receptor 2 expression, which facilitates parasite internalization. Nuclear factor kappa B (NFkB) pathway activation represents a required upstream event for L. amazonensis-induced LTB4 synthesis. These leishmanicidal mechanisms mediated by neutrophil-derived LTB4 act through activation of its receptor, B leukotriene receptor 1 (BLT1).
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation-FIOCRUZ Federal University of Bahia-UFBA, Salvador, Brazil.
authors.forename: Natalia Machado
authors.initials: NM
authors.lastname: Tavares
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation-FIOCRUZ Federal University of Bahia-UFBA, Salvador, Brazil.
authors.forename: Théo
authors.initials: T
authors.lastname: Araújo-Santos
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation-FIOCRUZ.
authors.forename: Lilian
authors.initials: L
authors.lastname: Afonso
authors.affiliation: René Rachou Research Center, Oswaldo Cruz Foundation-FIOCRUZ, Belo Horizonte, Brazil.
authors.forename: Paula Monalisa
authors.initials: PM
authors.lastname: Nogueira
authors.affiliation: Carlos Chagas Filho Institute-Federal University of Rio de Janeiro-UFRJ.
authors.forename: Ulisses Gazos
authors.initials: UG
authors.lastname: Lopes
authors.affiliation: René Rachou Research Center, Oswaldo Cruz Foundation-FIOCRUZ, Belo Horizonte, Brazil.
authors.forename: Rodrigo Pedro
authors.initials: RP
authors.lastname: Soares
authors.affiliation: Immunopharmacology Laboratory, Oswaldo Cruz Institute-Oswaldo Cruz Foundation-FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Patrícia Torres
authors.initials: PT
authors.lastname: Bozza
authors.affiliation: Carlos Chagas Filho Institute-Federal University of Rio de Janeiro-UFRJ.
authors.forename: Christianne
authors.initials: C
authors.lastname: Bandeira-Melo
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation-FIOCRUZ Federal University of Bahia-UFBA, Salvador, Brazil National Institute of Science and Technology for Immunology Investigation (iii-INCT), Salvador, Bahia, Brazil.
authors.forename: Valeria Matos
authors.initials: VM
authors.lastname: Borges
authors.affiliation: Gonçalo Moniz Research Center, Oswaldo Cruz Foundation-FIOCRUZ Federal University of Bahia-UFBA, Salvador, Brazil National Institute of Science and Technology for Immunology Investigation (iii-INCT), Salvador, Bahia, Brazil.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Brodskyn
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D006801:Humans; D007894:Leishmania mexicana / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; C513240:LTB4R protein, human; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018102:Receptors, Leukotriene B4; D051195:Toll-Like Receptor 2; D007975:Leukotriene B4
keywords: LPG; Leishmania amazonensis; TLR2; NFkB; human neutrophils; leukotriene B4