期刊
JOURNAL OF IMMUNOLOGY
卷 182, 期 4, 页码 2525-2531出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0802860
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- Institut National de la Sante et de la Recherche Medicale/Fundacao Oswaldo Cruz (INSERM/FIOCRUZ) Collaborative Program
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES)
- Programa Institucional de Bolsas de Iniciacao Cientifica (PIBIC)-FIOCRUZ
- Alban Program
- European Union Program of High Level Scholarships for Latin America [E06D103200BR]
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 asL. braziliensis infection, major human pathogens. The Journal of Immunology, 2009,182: 2525-2531.
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