| Author | Luz, Nivea Farias | |
| Author | Andrade, Bruno B. | |
| Author | Feijó, Daniel Ferreira | |
| Author | Araújo-Santos, Théo | |
| Author | Carvalho, Graziele Quintela de | |
| Author | Andrade, Daniela | |
| Author | Abánades, Daniel Ruiz | |
| Author | Melo, Enaldo Vieira de | |
| Author | Silva, Angela M. | |
| Author | Brodskyn, Claudia Ida | |
| Author | Barral-Netto, Manoel | |
| Author | Barral, Aldina | |
| Author | Soares, Rodrigo Pedro Pinto | |
| Author | Almeida, Roque Pacheco de | |
| Author | Bozza, Marcelo Torres | |
| Author | Borges, Valeria de Matos | |
| Access date | 2023-07-11T14:07:30Z | |
| Available date | 2023-07-11T14:07:30Z | |
| Document date | 2012 | |
| Citation | LUZ, Nivea Farias et al. Heme oxygenase-1 promotes the persistence of Leishmania chagasi infection. J Immunol., v. 188, n. 9, p. 4460-4467, 2012. doi: 10.4049/jimmunol.1103072. | en_US |
| ISSN | 0022-1767 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/59507 | |
| Language | eng | en_US |
| Publisher | American Association of Immunologists | en_US |
| Rights | restricted access | |
| Title | Heme Oxygenase-1 Promotes the Persistence of Leishmania chagasi Infection | en_US |
| Type | Article | |
| DOI | 10.4049/jimmunol.1103072 | |
| 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 Leishmatzia 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 Leishmatzia 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-alpha 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil | en_US |
| Affilliation | Immunobiology Section. Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, United States of America | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil | en_US |
| Affilliation | Department of Medicine. University Hospital. Universidade Federal de Sergipe. Aracaju, SE Brazil | en_US |
| Affilliation | Department of Medicine. University Hospital. Universidade Federal de Sergipe. Aracaju, SE Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil/ Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil/ Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil/ Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Department of Medicine. University Hospital. Universidade Federal de Sergipe. Aracaju, SE Brazil/Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brazil | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brazil/Universidade Federal da Bahia. Salvador, BA, Brazil/Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia. Salvador, BA, Brazil | en_US |
| Subject | Leishmania infantum chagasi | en_US |
| Subject | visceral leishmaniasis | en_US |
| Subject | macrophage heme oxygenase | en_US |
| Embargo date | 2099-12-31 | |
