Intranasal interleukin-12 treatment for protection against respiratory infection with the Francisella tularensis live vaccine strain
Intranasal interleukin-12 treatment for protection against respiratory infection with the Francisella tularensis live vaccine strain
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DOI：
10.1128/iai.73.4.2306-2311.2005
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Metzger, DW
中科院分区：
文献类型：
--
作者：
Duckett, NS;Olmos, S;Metzger, DW
土拉热弗朗西丝菌是一种革兰氏阴性细胞内细菌，可引起人类和啮齿动物致命的呼吸道感染。然而，对先天性或适应性免疫在呼吸道土拉菌病保护中的作用知之甚少。本研究探讨了白细胞介素-12（IL-12）在诱导小鼠肺保护性免疫中的作用。土拉菌进行了研究。发现γ干扰素（IFN-γ）和IL-12是严格需要的保护，因为缺乏IFN-γ、IL-12 p35或IL-12 p40的小鼠都死于对野生型小鼠亚致死的LVS剂量。此外，在用致死剂量的LVS（109000 CFU）鼻内感染之前，外源性IL-12治疗24显著降低野生型BALB/c和C57 BL/6小鼠的肺、肝和脾中的细菌负荷，并允许动物在感染中存活;在IFN-γ缺陷型小鼠中未观察到这种保护。IL-12诱导的对LVS感染的抵抗在NK细胞缺陷的beige小鼠中仍然观察到，但在CD 8（-/-）小鼠中没有观察到。这些结果表明，鼻内递送的外源性IL-12可以通过至少部分依赖于IFN-γ和CD 8 T细胞表达的机制来预防呼吸性土拉菌病。
Francisella tularensis is a gram-negative intracellular bacterium that can induce lethal respiratory infection in humans and rodents. However, little is known about the role of innate or adaptive immunity in protection from respiratory tularemia. In the present study, the role of interleukin-12 (IL-12) in inducing protective immunity in the lungs against intranasal infection of mice with the live vaccine strain (LVS) of F. tularensis was investigated. It was found that gamma interferon (IFN-gamma) and IL-12 were strictly required for protection, since mice deficient in IFN-gamma, IL-12 p35, or IL-12 p40 all succumbed to LVS doses that were sublethal for wild-type mice. Furthermore, exogenous IL-12 treatment 24 It before intranasal infection with a lethal dose of LVS (109000 CFU) significantly decreased bacterial loads in the lungs, livers, and spleens of wild-type BALB/c and C57BL/6 mice and allowed the animals to survive infection; such protection was not observed in IFN-gamma deficient mice. The resistance induced by IL-12 to LVS infection was still observed in NK cell-deficient beige mice but not in CD8(-/-) mice. These results demonstrate that exogenous IL-12 delivered intranasally can prevent respiratory tularemia through a mechanism that is at least partially dependent upon the expression of IFN-gamma and CD8 T cells.