Heme Oxygenase-1 promotes the persistence of Leishmania chagasi infection

dc.creatorLuz, Nívea Farias
dc.creatorAndrade, Bruno de Bezerril
dc.creatorFeijó, Daniel F
dc.creatorSantos, Théo de Araújo
dc.creatorCarvalho, Graziele Quintela de
dc.creatorAndrade, Daniela
dc.creatorAbánades, Daniel Ruiz
dc.creatorMelo, Enaldo V
dc.creatorSilva, Angela M
dc.creatorBrodskyn, Claudia Ida
dc.creatorBarral Netto, Manoel
dc.creatorBarral, Aldina Maria Prado
dc.creatorSoares, Rodrigo Pedro
dc.creatorAlmeida, Roque Pacheco de
dc.creatorBozza, Marcelo Torres
dc.creatorBorges, Valeria de Matos
dc.date2013-12-04T15:54:24Z
dc.date2013-12-04T15:54:24Z
dc.date2012
dc.date.accessioned2023-09-26T22:53:32Z
dc.date.available2023-09-26T22:53:32Z
dc.identifierLUZ, 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.
dc.identifier0022-1767
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/7275
dc.identifier10.4049/jimmunol.1103072
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8884441
dc.descriptionVisceral 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
dc.formatapplication/pdf
dc.languageeng
dc.publisherThe American Association of Immunologists, Inc.,
dc.rightsopen access
dc.subjectLeishmania
dc.subjectLeishmaniose Visceral
dc.subjectLeishmania infantum
dc.subjectInfecção
dc.subjectCamundongos
dc.titleHeme Oxygenase-1 promotes the persistence of Leishmania chagasi infection
dc.typeArticle


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