Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance.
Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance.
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DOI：
10.1111/j.1365-2958.2008.06528.x
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发表时间：
2009-01
影响因子：
3.6
通讯作者：
Kuchler K
中科院分区：
文献类型：
--
作者：
Frohner IE;Bourgeois C;Yatsyk K;Majer O;Kuchler K
哺乳动物的天然免疫细胞在氧化爆发反应中产生活性氧种(ROS)，以消灭入侵的微生物病原体。使用实时定量ROS分析，我们在这里表明，酵母和丝状形式的人类真菌病原体白色念珠菌都能在原始天然免疫细胞(如巨噬细胞和树突状细胞)中触发ROS的产生。通过反向遗传方法，我们证明了巨噬细胞或髓系树突状细胞与缺乏超氧化物歧化酶(SOD)Sod5的白色念珠菌细胞共培养会在体外导致大量的胞外ROS积聚。在与不含Sod4和Sod5的真菌细胞共培养时，ROS的积累进一步增加。存活实验表明，缺乏Sod5和Sod4的白色念珠菌突变株在体外巨噬细胞存在下表现出严重的生存能力丧失。与野生型相比，Sod5Δ/Δ和Sod4Δ/ΔSod5Δ/Δ突变体的活性降低并不明显，gp91Phox−/−小鼠的巨噬细胞具有氧化爆发活性缺陷，表明巨噬细胞对真菌病原体具有ROS依赖的杀伤活性。这些数据显示了细胞表面SOD在解毒ROS方面的生理作用，并表明了一种机制，即白色念珠菌，可能还有许多其他微生物病原体，可以逃避体内的宿主免疫监视。
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 sod5Δ/Δ and sod4Δ/Δsod5Δ/Δ 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.
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DOI：
10.1086/523110
发表时间：
2007-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Gow NA;Netea MG;Munro CA;Ferwerda G;Bates S;Mora-Montes HM;Walker L;Jansen T;Jacobs L;Tsoni V;Brown GD;Odds FC;Van der Meer JW;Brown AJ;Kullberg BJ
通讯作者：
Kullberg BJ
影响因子：
4.4
作者：
Jouault, Thierry;Behi, Miryam El Abed-El;Poulain, Daniel
通讯作者：
Poulain, Daniel
影响因子：
2.6
作者：
Hwang, CS;Baek, YU;Kang, SO
通讯作者：
Kang, SO
DOI：
10.1073/pnas.94.25.13997
发表时间：
1997-12-09
影响因子：
11.1
作者：
DeGroote, MA;Ochsner, UA;Fang, FC
通讯作者：
Fang, FC
影响因子：
7.4
作者：
Lundqvist, H;Dahlgren, C
通讯作者：
Dahlgren, C