Journal of Immunology

Texto completo: acesso restrito. p. 4460-4467 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-11T13:43:08Z No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Rejected by Delba Rosa (delba@ufba.br), reason: Por gentileza, Cite todos os autores; O endereço eletrônico não confere. Grata on 2014-10-09T16:03:14Z (GMT) Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-10-14T11:18:15Z No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2014-10-14T12:13:10Z (GMT) No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Made available in DSpace on 2014-10-14T12:13:10Z (GMT). No. of bitstreams: 1 Nívea F. Luz.pdf: 1584833 bytes, checksum: aeb0961f7c6201b1a38868d69549901f (MD5) Previous issue date: 2012 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-α 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.