Author | Cunha, Antonio Ricardo Khouri | |
Author | Bafica, Andre Luiz Barbosa | |
Author | Silva, Maria da Purificação Pereira | |
Author | Noronha, Almério Libório Lopes de | |
Author | Kolb, Jean Pierre | |
Author | Wietzerbin, Juana | |
Author | Barral, Aldina Maria Prado | |
Author | Barral Netto, Manoel | |
Author | Weyenbergh, Johan Van | |
Access date | 2011-04-13T00:00:14Z | |
Available date | 2011-04-13T00:00:14Z | |
Document date | 2009 | |
Citation | KHOURI, R. et al. IFN-beta impairs superoxide-dependent parasite killing in human macrophages: evidence for a deleterious role of SOD1 in cutaneous leishmaniasis. Journal of Immunology, v. 182, n. 4, p. 2525-2531, 2009. | pt_BR |
ISSN | 0022-1767 | |
URI | https://www.arca.fiocruz.br/handle/icict/1893 | |
Language | eng | pt_BR |
Rights | open access | en |
Title | IFN-beta impairs superoxide-dependent parasite killing in human macrophages: evidence for a deleterious role of SOD1 in cutaneous leishmaniasis | pt_BR |
Type | Article | pt_BR |
DOI | 10.4049/jimmunol.0802860 | |
Abstract | Type I IFNs (IFN-alpha/beta) have only recently gained considerable attention as immunomodulators in nonviral infectious diseases. IFN-beta has been shown to protect, in a NO-dependent manner, against murine Old World leishmaniasis caused by Leishmania major, but data in New World leishmaniasis are lacking. We found that IFN-beta dose-dependently increases parasite burden in Leishmania amazonensis- as well as Leishmania braziliensis-infected human macrophages, independent of endogenous or exogenous NO. However, IFN-beta significantly reduced superoxide release in Leishmania-infected as well as uninfected human macrophages. This decrease in superoxide production was paralleled by a significant IFN-beta-mediated increase in superoxide dismutase 1 (SOD1) protein levels. Additionally, IFN-beta inhibition of leishmanicidal activity was mimicked by SOD1 and antagonized by either pharmacological or small interfering RNA-mediated inhibition of SOD1. Finally, pronounced SOD1 expression in situ was demonstrated in biopsies from New World cutaneous leishmaniasis patients. These findings reveal a hitherto unknown IFN-beta/SOD1 axis in Leishmania infection and suggest that inhibition of SOD-associated pathways could serve as strategy in the treatment of L. amazonensis as well as L. braziliensis infection, major human pathogens. | pt_BR |
Affilliation | Laboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, Brasil | pt_BR |
Affilliation | Laboratório de Imunoparasitologia. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, Brasil | pt_BR |
Affilliation | Laboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, Brasil | pt_BR |
Affilliation | Laboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, Brasil | pt_BR |
Affilliation | Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé 872, Centre de Recherche des Cordeliers, Paris, França | pt_BR |
Affilliation | INSERM, Unité 365, Institut Curie, Paris, França | pt_BR |
Affilliation | Laboratório de Imunoparasitologia. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, Brasil | pt_BR |
Affilliation | Laboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, Brasil | pt_BR |
Affilliation | Laboratório Integrado de Microbiologia e Imunoregulação. Centro de Pesquisas Gonçalo Moniz - FIOCRUZ, Bahia, Brasil | pt_BR |
DeCS | Imunoistoquímica Interferon beta | pt_BR |
DeCS | Leishmaniose Cutânea | pt_BR |
DeCS | Macrófagos | pt_BR |
DeCS | Superóxido Dismutase | pt_BR |
DeCS | Superóxidos/IM | pt_BR |