Title:	Understanding the mechanisms controlling Leishmania amazonensis infection In vitro: the role of LTB4 derived from human neutrophils.
Authors:	Tavares, Natalia Machado Santos, Théo de Araújo Afonso, Lilian Maria Nogueira, Paula Monalisa Lopes, Ulisses Gazos Soares, Rodrigo Pedro Bozza, Patrícia Torres Bandeira-Melo, Christianne Borges, Valeria de Matos Brodskyn, Claudia Ida
Affilliation:	Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil Federal University of Rio de Janeiro. UFRJ.Carlos Chagas Filho Institute. Rio de Janeiro, RJ, Brasil Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil Federal University of Rio de Janeiro. UFRJ.Carlos Chagas Filho Institute. Rio de Janeiro, RJ, Brasil Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / National Institute of Science and Technology for Immunology Investigation (iii–INCT). Salvador, BA, Brasil Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / National Institute of Science and Technology for Immunology Investigation (iii–INCT). Salvador, BA, Brasil
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)
Keywords:	Leishmania amazonensis LPG Human neutrophils Leukotriene B4 TLR2 NFkB
Issue Date:	2014
Publisher:	Oxford University Press
Citation:	TAVARES, N. M. et al. Understanding the mechanisms controlling Leishmania amazonensis infection In vitro: the role of LTB4 derived from human neutrophils. Journal of Infectious Disease, v. 210, n. 4, p. 656-666, 2014.
DOI:	10.1093/infdis/jiu158
ISSN:	1537-6613
Copyright:	open access
Appears in Collections:	MG - IRR - Artigos de Periódicos IOC - Artigos de Periódicos BA - IGM - Artigos de Periódicos

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