T Cells from Lungs and Livers of Francisella tularensis-Immune Mice Control the Growth of Intracellular Bacteria
T Cells from Lungs and Livers of Francisella tularensis-Immune Mice Control the Growth of Intracellular Bacteria
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DOI：
10.1128/iai.01322-08
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发表时间：
2009-05-01
影响因子：
3.1
通讯作者：
Elkins, Karen L.
中科院分区：
文献类型：
--
作者：
Collazo, Carmen M.;Meierovics, Anda I.;Elkins, Karen L.
已经用活疫苗株(LVS)在小鼠模型上研究了细胞内细菌Francisella tularensis的非肠道和呼吸道疫苗接种，免疫小鼠的脾细胞经常用于免疫学研究。然而，在非淋巴器官中，宿主免疫反应的机制可能不同，非淋巴器官是感染的重要部位，如肺和肝脏。使用肠外(皮内)或呼吸道(云雾)疫苗接种，我们在这里分别检查产生的LVS免疫肝或肺细胞的功能。令人惊讶的是，用云雾雾化给药时，LVS的毒力比经鼻滴注的要大得多，这表明初始定位和/或传播模式取决于方法的差异。只有低剂量是亚致死性的，亚致死性云雾感染的解决取决于干扰素(干扰素)、肿瘤坏死因子α和诱导型一氧化氮合酶。然而，云雾或肠外感染的存活导致了对致死性LVS腹膜内或气溶胶攻击的保护性免疫反应的发展，反映了这两种情况下系统次级免疫的发展。通过在体外直接检测LVS免疫肺或肝淋巴细胞的功能来进一步检测这种免疫。由呼吸道感染引发的肺淋巴细胞和由非肠道感染引发的肝淋巴细胞在体外明显地控制了细胞内细菌的生长，主要是通过不依赖于干扰素-γ活性的机制。因此，我们的结果表明，免疫T细胞存在于LVS免疫小鼠的脾、肝和肺的功能相似之处。
Parenteral and respiratory vaccinations with the intracellular bacterium Francisella tularensis have been studied using the live vaccine strain (LVS) in a mouse model, and spleen cells from immune mice are often used for immunological studies. However, mechanisms of host immunological responses may be different in non-lymphoid organs that are important sites of infection, such as lung and liver. Using parenteral (intradermal) or respiratory (cloud aerosol) vaccination, here we examine the functions of resulting LVS-immune liver or lung cells, respectively. Surprisingly, LVS was considerably more virulent when administered by cloud aerosol than by intranasal instillation, suggesting method-dependent differences in initial localization and/or dissemination patterns. Only low doses were sublethal, and resolution of sublethal cloud aerosol infection was dependent on gamma interferon (IFN-gamma), tumor necrosis factor alpha, and inducible nitric oxide synthase. Nonetheless, survival of cloud aerosol or parenteral infection resulted in the development of a protective immune response against lethal LVS intraperitoneal or aerosol challenge, reflecting development of systemic secondary immunity in both cases. Such immunity was further detected by directly examining the functions of LVS-immune lung or liver lymphocytes in vitro. Lung lymphocytes primed by respiratory infection, as well as liver lymphocytes primed by parenteral infection, clearly controlled in vitro intracellular bacterial growth primarily via mechanisms that were not dependent on IFN-gamma activity. Thus, our results indicate functional similarities between immune T cells residing in spleens, livers, and lungs of LVS-immune mice.