Author | Carvalho, Graziele Quintela | |
Author | Luz, Nívea Farias | |
Author | Celes, Fabiana Santana | |
Author | Zanette, Dalila Lucíola | |
Author | Andrade, Daniela Rodrigues | |
Author | Menezes, Diego Silva | |
Author | Tavares, Natália M | |
Author | Brodskyn, Claudia Ida | |
Author | Prates, Deboraci Brito | |
Author | Gonçalves, Marilda de Souza | |
Author | Oliveira, Camila Indiani de | |
Author | Almeida, Roque Pacheco de | |
Author | Bozza, Marcelo Torres | |
Author | Andrade, Bruno de Bezerril | |
Author | Borges, Valeria de Matos | |
Access date | 2018-02-08T14:05:11Z | |
Available date | 2018-02-08T14:05:11Z | |
Document date | 2017 | |
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. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/24775 | |
Sponsorship | Fundação de Amparo à Pesquisa do Estado da Bahia-FAPESB (RED0018/2013 to VB) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq (478480/2013-0 to VB, 552721/2011-5 and
019.203.02712/2009-8 FAPITEC/CNPq to RA). RA also received a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES: 23038.005304/2011-01). GQ-C received
a fellowship from FAPESB. | pt_BR |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmania infantum | pt_BR |
Subject in Portuguese | Heme | pt_BR |
Subject in Portuguese | Ferro | pt_BR |
Subject in Portuguese | Neutrófilos | pt_BR |
Subject in Portuguese | Morte celular | pt_BR |
Subject in Portuguese | Heme oxigenase 1 | pt_BR |
Title | Heme Drives Oxidative Stress-Associated Cell Death in Human Neutrophils Infected with Leishmania infantum | pt_BR |
Type | Article | pt_BR |
DOI | 10.3389/fimmu.2017.01620 | |
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. | pt_BR |
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 | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Instituto de Tecnologia e Pesquisa. Aracaju, SE, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Biomorfologia. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Departamento de Medicina. Aracaju, SE, Brasil | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil | pt_BR |
Subject | Leishmania infantum | pt_BR |
Subject | Heme | pt_BR |
Subject | Iron | pt_BR |
Subject | Neutrophils | pt_BR |
Subject | Cell death | pt_BR |
Subject | Heme oxygenase 1 | pt_BR |