Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/24775
Title: Heme Drives Oxidative Stress-Associated Cell Death in Human Neutrophils Infected with Leishmania infantum
Authors: Carvalho, Graziele Quintela
Luz, Nívea Farias
Celes, Fabiana Santana
Zanette, Dalila Lucíola
Andrade, Daniela Rodrigues
Menezes, Diego Silva
Tavares, Natália M
Brodskyn, Claudia Ida
Prates, Deboraci Brito
Gonçalves, Marilda de Souza
Oliveira, Camila Indiani de
Almeida, Roque Pacheco de
Bozza, Marcelo Torres
Andrade, Bruno de Bezerril
Borges, Valeria de Matos
Affilliation: Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Instituto Federal de Educação, Ciência e Tecnologia Baiano. Santa Inês, Ba, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Instituto de Tecnologia e Pesquisa. Aracaju, SE, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biomorfologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal de Sergipe. Hospital Universitário. Departamento de Medicina. Aracaju, SE, Brasil
Universidade Federal do Rio de Janeiro. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brazil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Abstract: Free heme is an inflammatory molecule capable of inducing migration and activation of neutrophils. Here, we examine the heme-driven oxidative stress-associated cell death mechanisms in human neutrophils infected with Leishmania infantum, an etiologic agent of visceral leishmaniasis (VL). We first performed exploratory analyses in a population of well characterized treatment-naïve VL patients as well as uninfected controls, who were part of previously reported studies. We noted a positive correlation between serum concentrations of heme with heme oxygenase-1 (HO-1) and lactate deydrogenase, as well as, a negative correlation between heme values and peripheral blood neutrophils counts. Moreover, in vitro infection with L. infantum in the presence of heme enhanced parasite burden in neutrophils, while increasing the production of reactive oxygen species and release of neutrophilic enzymes. Additional experiments demonstrated that treatment of infected neutrophils with ferrous iron (Fe+2), a key component of the heme molecule, resulted in increased parasite survival without affecting neutrophil activation status. Furthermore, stimulation of infected neutrophils with heme triggered substantial increases in HO-1 mRNA expression as well as in superoxide dismutase-1 enzymatic activity. Heme, but not Fe+2, induced oxidative stress-associated cell death. These findings indicate that heme promotes intracellular L. infantum survival via activation of neutrophil function and oxidative stress. This study opens new perspectives for the understanding of immunopathogenic mechanisms involving neutrophils in VL.
Keywords: Leishmania infantum
Heme
Iron
Neutrophils
Cell death
Heme oxygenase 1
keywords: Leishmania infantum
Heme
Ferro
Neutrófilos
Morte celular
Heme oxigenase 1
Issue Date: 2017
Publisher: Frontiers Media
Citation: CARVALHO, G. Q. et al. Heme Drives Oxidative Stress-Associated Cell Death in Human Neutrophils Infected with Leishmania infantum. Frontiers in Immunology, v. 8, p.1620, 2017.
DOI: 10.3389/fimmu.2017.01620
ISSN: 1664-3224
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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