Mechanism of high susceptibility of iron-overloaded mouse to Vibrio vulnificus infection
Mechanism of high susceptibility of iron-overloaded mouse to Vibrio vulnificus infection
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DOI：
10.1111/j.1348-0421.2000.tb02577.x
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发表时间：
2000-01-01
影响因子：
2.6
通讯作者：
Ou, JT
中科院分区：
文献类型：
--
作者：
Hor, LI;Chang, YK;Ou, JT
创伤弧菌会在患有潜在疾病的人类中产生暴发性败血症，特别是那些患有铁水平升高疾病的人。因此，在用右旋糖酐铁治疗的小鼠中研究了高铁水平对创伤弧菌毒力的影响。铁负载的小鼠对创伤弧菌感染高度敏感，当经腹膜感染时，LD50（50%致死剂量）降低了5个对数。然而，当通过口服途径感染时，LD50影响很小，除非小鼠用其他药物（如环磷酰胺或D-半乳糖胺）治疗。当血液中细菌浓度达到10（5）cfu/ml或以上时，有或没有铁超载的小鼠死亡。铁增加了动物体内和体外细菌的生长速度，在铁超载的小鼠中很快达到致死浓度。在添加或不添加铁的情况下生长的创伤弧菌，在高细菌浓度下对分离的细胞或动物体内表现出强烈的细胞毒性。在感染细菌（可能是由内毒素引起）的小鼠中，铁超载会刺激肿瘤坏死因子α（TNF-α）的产生，这是感染性休克的主要因素；然而，中性粒细胞的迁移受到 TNF-α 的影响，似乎不太活跃。综合起来，创伤弧菌的主要毒力因素似乎是细菌的加速生长以迅速达到致死水平，以及由于铁超载而导致包括中性粒细胞在内的免疫细胞活性降低，这两种效应体现了宿主和细菌的其他毒力因素。除了内毒素刺激的TNF-α之外，这些因子增强细胞毒性，杀死宿主细胞，包括宿主的免疫细胞。
Vibrio vulnificus produces fulminant septicemia in humans with underlying conditions, particularly those with diseases that elevate the iron level. The effect of a high iron level on the virulence of V. vulnificus was therefore investigated in mice treated with iron dextran, The mice loaded with iron became highly susceptible to V. vulnificus infection, the LD50 (50% lethal dose) decreased five logs when infected per peritoneum, However, when infected via the oral route, the LD50 was affected little unless the mouse was treated with an additional drug such as cyclophosphamide or D-galactosamine. Mice with or without iron-overloading died when the bacterial concentration in the blood reached 10(5) cfu/ml or above. Iron increased the growth rate of the bacteria, both inside and outside of the animal, quickly reaching a lethal concentration in the iron-overloaded mouse. V. vulnificus, grown with or without the addition of iron, showed strong cytotoxicity on the isolated cells or within the animal at high bacterial concentration, Iron overload stimulated the production of tumor necrosis factor alpha (TNF-alpha), a major factor of septic shock, in mice upon infection with the bacteria, probably caused by the endotoxin; however, the neutrophils, whose migration is effected by TNF-alpha, appeared to be less active. Taken together, the major virulence factor of V. vulnificus appeared to be the accelerated growth of bacteria to quickly reach the lethal level and the lower activity of immune cells including neutrophil as a result of iron-overloading, These two effects manifest other virulence factors, the host's as well as bacterial. Such factors, other than TNF-alpha stimulated by the endotoxin, enhanced cytotoxicity, which kills the host cells including the host's immune cells.