Author | Luz, Nívea Farias | |
Author | Andrade, Bruno de Bezerril | |
Author | Feijó, Daniel F | |
Author | Santos, Théo de Araújo | |
Author | Carvalho, Graziele Quintela de | |
Author | Andrade, Daniela | |
Author | Abánades, Daniel Ruiz | |
Author | Melo, Enaldo V | |
Author | Silva, Angela M | |
Author | Brodskyn, Claudia Ida | |
Author | Barral Netto, Manoel | |
Author | Barral, Aldina Maria Prado | |
Author | Soares, Rodrigo Pedro | |
Author | Almeida, Roque Pacheco de | |
Author | Bozza, Marcelo Torres | |
Author | Borges, Valeria de Matos | |
Access date | 2013-12-04T15:54:24Z | |
Available date | 2013-12-04T15:54:24Z | |
Document date | 2012 | |
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. | pt_BR |
ISSN | 0022-1767 | |
URI | https://www.arca.fiocruz.br/handle/icict/7275 | |
Language | eng | pt_BR |
Publisher | The American Association of Immunologists, Inc., | pt_BR |
Rights | open access | pt_BR |
Title | Heme Oxygenase-1 promotes the persistence of Leishmania chagasi infection | pt_BR |
Type | Article | pt_BR |
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 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 | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | National Institute of Allergy and Infectious Diseases. National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, MD | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil | pt_BR |
Affilliation | Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | Fundação OSwaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil / Universidade Federal de Sergipe. University Hospital. Department of Medicine. Aracaju, SE, Brasil | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | 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 | pt_BR |
DeCS | Leishmania | pt_BR |
DeCS | Leishmaniose Visceral | pt_BR |
DeCS | Leishmania infantum | pt_BR |
DeCS | Infecção | pt_BR |
DeCS | Camundongos | pt_BR |