{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:04:27Z","timestamp":1791551067666,"version":"4.3.4"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03b1 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1103072","type":"journal-article","created":{"date-parts":[[2012,3,30]],"date-time":"2012-03-30T00:31:28Z","timestamp":1333067488000},"page":"4460-4467","source":"Crossref","is-referenced-by-count":88,"title":["Heme Oxygenase-1 Promotes the Persistence of <i>Leishmania chagasi<\/i> Infection"],"prefix":"10.1093","volume":"188","author":[{"given":"N\u00edvea F","family":"Luz","sequence":"first","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno B","family":"Andrade","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F","family":"Feij\u00f3","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro , Rio de Janeiro 21941-590 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9o","family":"Ara\u00fajo-Santos","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziele Q","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Andrade","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R","family":"Ab\u00e1nades","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enaldo V","family":"Melo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital, Universidade Federal de Sergipe , Aracaju 49010-390 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital, Universidade Federal de Sergipe , Aracaju 49010-390 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia I","family":"Brodskyn","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Investiga\u00e7\u00e3o em Imunologia , Salvador, Bahia 40110-100 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoel","family":"Barral-Netto","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Investiga\u00e7\u00e3o em Imunologia , Salvador, Bahia 40110-100 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldina","family":"Barral","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade Federal da Bahia , Salvador 40110-060 ,","place":["Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Investiga\u00e7\u00e3o em Imunologia , Salvador, Bahia 40110-100 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo P","family":"Soares","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou\/Funda\u00e7\u00e3o Oswaldo Cruz , Belo Horizonte 30190-002 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roque P","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital, Universidade Federal de Sergipe , Aracaju 49010-390 ,","place":["Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Investiga\u00e7\u00e3o em Imunologia , Salvador, Bahia 40110-100 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo T","family":"Bozza","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro , Rio de Janeiro 21941-590 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria M","family":"Borges","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz\/Funda\u00e7\u00e3o Oswaldo Cruz , Salvador 40295-001 ,","place":["Brazil"]},{"name":"Universidade 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