Distinct roles of reactive nitrogen and oxygen species to control infection with the facultative intracellular bacterium Francisella tularensis
Distinct roles of reactive nitrogen and oxygen species to control infection with the facultative intracellular bacterium Francisella tularensis
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DOI：
10.1128/iai.72.12.7172-7182.2004
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发表时间：
2004-12-01
影响因子：
3.1
通讯作者：
Sjöstedt, A
中科院分区：
文献类型：
--
作者：
Lindgren, H;Stenmark, S;Sjöstedt, A
活性氮类（RNS）和活性氧类（ROS）是杀菌宿主反应的重要介质。我们研究了这两种介质的贡献，以控制感染的兼性细胞内细菌土拉热弗朗西丝菌。当皮内感染活疫苗株F。在土拉热LVS中，RNS产生缺陷的小鼠（iNOS（-/-）小鼠）或吞噬细胞氧化酶产生缺陷的小鼠（p47（phox-/-）小鼠）表现出对感染的抵抗力受损。对于野生型小鼠，iNOS（-/-）小鼠的50%致死剂量（LD 50）为500，000 CFU。iNOS（-/-）小鼠存活26.4 +/- 1.8天，p47（phox-/-）小鼠存活10.1 +/- 1.3天。在感染过程中，血清γ干扰素（IFN-γ）和白细胞介素-6（IL-6）水平在iNOS（-/-）和p47（phox-/-）小鼠中高于野生型小鼠。iNOS（-/-）小鼠的肝脏组织学检查显示严重的肝脏病理。初次感染后5周，从经抗肿瘤治疗的iNOS（-/-）小鼠中获得的脾细胞显示出体外回忆反应，与从野生型小鼠中获得的细胞相比，该反应的幅度相似，IFN-γ的分泌量更大。总之，缺乏RNS或ROS表达的小鼠对F.土拉菌RNS和ROS的作用似乎是不同的，因为小鼠缺乏生产的ROS表现出传播的感染，并在感染的早期阶段死亡，而RNS缺乏导致严重的肝脏病理和感染的收缩过程。
Reactive nitrogen species (RNS) and reactive oxygen species (ROS) are important mediators of the bactericidal host response. We investigated the contribution of these two mediators to the control of infection with the facultative intracellular bacterium Francisella tularensis. When intradermally infected with the live vaccine strain F. tularensis LVS, mice deficient in production of RNS (iNOS(-/-) mice) or in production of ROS by the phagocyte oxidase (p47(phox-/-) mice) showed compromised resistance to infection. The 50% lethal dose (LD50) for iNOS(-/-) mice was 500,000 CFU for wild-type mice. The iNOS(-/-) mice survived for 26.4 +/- 1.8 days, and the p47(phox-/-) mice survived for 10.1 +/- 1.3 days. During the course of infection, the serum levels of gamma interferon (IFN-gamma) and interleukin-6 were higher in iNOS(-/-) and p47(phox-/-) mice than in wild-type mice. Histological examination of livers of iNOS(-/-) mice revealed severe liver pathology. Splenocytes obtained 5 weeks after primary infection from antibiotic-treated iNOS(-/-) mice showed an in vitro recall response that was similar in magnitude and greater secretion of IFN-gamma compared to cells obtained from wild-type mice. In summary, mice lacking expression of RNS or ROS showed extreme susceptibility to infection with F. tularensis LVS. The roles of RNS and ROS seemed to be distinct since mice deficient in production of ROS showed dissemination of infection and died during the early phase of infection, whereas RNS deficiency led to severe liver pathology and a contracted course of infection.