Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7275
Title: Heme Oxygenase-1 promotes the persistence of Leishmania chagasi infection
Authors: Luz, Nívea Farias
Andrade, Bruno de Bezerril
Feijó, Daniel F
Santos, Théo de Araújo
Carvalho, Graziele Quintela de
Andrade, Daniela
Abánades, Daniel Ruiz
Melo, Enaldo V
Silva, Angela M
Brodskyn, Claudia Ida
Barral Netto, Manoel
Barral, Aldina Maria Prado
Soares, Rodrigo Pedro
Almeida, Roque Pacheco de
Bozza, Marcelo Torres
Borges, Valeria de Matos
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil
National Institute of Allergy and Infectious Diseases. National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, MD
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, 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 / 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 / Universidade Federal da Bahia. Salvador, BA, Brasil
Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil
Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil
Fundação OSwaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil / Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brasil
Abstract: Visceral leishmaniasis (VL) remains a major public health problem worldwide. This disease is highly associated with chronic inflammation and a lack of the cellular immune responses against Leishmania. It is important to identify major factors driving the successful establishment of the Leishmania infection to develop better tools for the disease control. Heme oxygenase-1 (HO-1) is a key enzyme triggered by cellular stress, and its role in VL has not been investigated. In this study, we evaluated the role of HO-1 in the infection by Leishmania infantum chagasi, the causative agent of VL cases in Brazil. We found that L. chagasi infection or lipophosphoglycan isolated from promastigotes triggered HO-1 production by murine macrophages. Interestingly, cobalt protoporphyrin IX, an HO-1 inductor, increased the parasite burden in both mouse and human-derived macrophages. Upon L. chagasi infection, macrophages from Hmox1 knockout mice presented significantly lower parasite loads when compared with those from wild-type mice. Furthermore, upregulation of HO-1 by cobalt protoporphyrin IX diminished the production of TNF-a and reactive oxygen species by infected murine macrophages and increased Cu/Zn superoxide dismutase expression in human monocytes. Finally, patients with VL presented higher systemic concentrations of HO-1 than healthy individuals, and this increase of HO-1 was reduced after antileishmanial treatment, suggesting that HO-1 is associated with disease susceptibility. Our data argue that HO-1 has a critical role in the L. chagasi infection and is strongly associated with the inflammatory imbalance during VL. Manipulation of HO-1 pathways during VL could serve as an adjunctive therapeutic approach
DeCS: Leishmania
Leishmaniose Visceral
Leishmania infantum
Infecção
Camundongos
Issue Date: 2012
Publisher: The American Association of Immunologists, Inc.,
Citation: LUZ, N. F. et al. Heme Oxygenase-1 promotes the persistence of Leishmania chagasi infection. Journal of Immunology, v.188, n. 9, p. 4460-4467, 2012.
DOI: 10.4049/jimmunol.1103072
ISSN: 0022-1767
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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