Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance.
Mammalian innate immune cells produce reactive oxygen species (ROS) in the oxidative burst reaction to destroy invading microbial pathogens. Using quantitative real-time ROS assays, we show here that both yeast and filamentous forms of the opportunistic human fungal pathogen Candida albicans trigger ROS production in primary innate immune cells such as macrophages and dendritic cells. Through a reverse genetic approach, we demonstrate that coculture of macrophages or myeloid dendritic cells with C. albicans cells lacking the superoxide dismutase (SOD) Sod5 leads to massive extracellular ROS accumulation in vitro. ROS accumulation was further increased in coculture with fungal cells devoid of both Sod4 and Sod5. Survival experiments show that C. albicans mutants lacking Sod5 and Sod4 exhibit a severe loss of viability in the presence of macrophages in vitro. The reduced viability of sod5Delta/Delta and sod4Delta/Deltasod5Delta/Delta mutants relative to wild type is not evident with macrophages from gp91phox(-/-) mice defective in the oxidative burst activity, demonstrating a ROS-dependent killing activity of macrophages targeting fungal pathogens. These data show a physiological role for cell surface SODs in detoxifying ROS, and suggest a mechanism whereby C. albicans, and perhaps many other microbial pathogens, can evade host immune surveillance in vivo.
Frohner
Ingrid E
IE
Medical University Vienna, Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories, Campus Vienna Biocenter; A-1030 Vienna, Austria.
Bourgeois
Christelle
C
Yatsyk
Kristina
K
Majer
Olivia
O
Kuchler
Karl
K
D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D012331:RNA, Fungal / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D005656:Fungal Proteins; D012331:RNA, Fungal; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase