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Title: IFN-beta Impairs Superoxide-Dependent Parasite Killing in Human Macrophages: Evidence for a Deleterious Role of SOD1 in Cutaneous Leishmaniasis
Authors: Khouri, Ricardo
Bafica, Andre
Pereira Silva, Maria da Purificacao
Noronha, Almerio
Kolb, Jean-Pierre
Wietzerbin, Juana
Barral, Aldina
Barral-Netto, Manoel
Van Weyenbergh, Johan # ×
Issue Date: Feb-2009
Publisher: Amer assoc immunologists
Series Title: Journal of Immunology vol:182 issue:4 pages:2525-2531
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 asL. braziliensis infection, major human pathogens. The Journal of Immunology, 2009,182: 2525-2531.
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical and Epidemiological Virology (Rega Institute)
× corresponding author
# (joint) last author

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