EXPERIMENTAL MURINE TULAREMIA CAUSED BY FRANCISELLA-TULARENSIS, LIVE VACCINE STRAIN - A MODEL OF ACQUIRED CELLULAR-RESISTANCE
EXPERIMENTAL MURINE TULAREMIA CAUSED BY FRANCISELLA-TULARENSIS, LIVE VACCINE STRAIN - A MODEL OF ACQUIRED CELLULAR-RESISTANCE
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DOI：
10.1016/0882-4010(87)90110-0
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发表时间：
1987-01-01
影响因子：
3.8
通讯作者：
KONGSHAVN, PAL
中科院分区：
文献类型：
--
作者：
ANTHONY, LSD;KONGSHAVN, PAL
我们使用土拉热弗朗西丝菌活疫苗株建立了实验诱导的小鼠土拉菌病模型。该微生物的亚致死性静脉接种导致C57 BL/6品系小鼠急性感染，持续约12天。弗朗西斯菌从血流中的清除显示在感染后5.5小时完成。此时，从脾脏中分离出的细菌数量大约是从肝脏中分离出的细菌数量的两倍。从初次感染中恢复的小鼠表现出对自体弗朗西斯菌再次感染的显著抗性，这种记忆持续至少15周。通过非贴壁脾细胞，感染小鼠对实验性兔热病的抵抗力可以被动地转移到未感染小鼠。能够过继转移抗性的细胞在感染后7天以最大浓度存在，并且在感染后至少20天内在脾细胞群中持续大量存在。当在肝脏中测量时，用来自恢复动物的血清处理小鼠引起电阻降低，并且当在脾脏中测量时，电阻增加。在感染期间通过用环孢菌素A治疗抑制T细胞介导的免疫导致组织细菌计数的急剧增加。环孢菌素A诱导的抗土拉菌耐药性抑制在感染后2-3天首次观察到，并保持明显至少8天。这些实验的结果表明，对实验性鼠土拉菌病的抗性主要由细胞介导的机制介导。这种机制涉及早在感染后2-3天就被激活的T细胞。因此，土拉热弗朗西丝菌的实验性非致死性感染是研究获得性细胞免疫机制的极好模型。
We have established a model of experimentally-induced tularemia in mice, using the live vaccine strain of Francisella tularensis. A sublethal, intravenous inoculation of this organism caused in C57BL/6 strain mice an acute infection which lasted approximately 12 days. The clearance of Francisella from the bloodstream was shown to be complete by 5.5 hours post-infection. At this time, approximately twice as many bacteria were isolated from the spleen as from the liver. Mice which had recovered from a primary infection demonstrated a significant resistance to re-infection with autologous Francisella, a memory which persisted for at least 15 weeks. Resistance to experimental tularemia could be passively transferred from infected mice to naive mice by means of non-adherent spleen cells. Cells capable of adoptive transfer of resistance were present at a maximal concentration 7 days following infection, and persisted in significant numbers within the spleen cell population for at least 20 days after infection. Treatment of mice with serum from recovered animals caused a decrease in resistance when measured in the livers, and an increase in resistance when measured in the spleens. Suppression of T cell-mediated immunity during infection by treatment with cyclosporin A resulted in a dramatic increase in the tissue bacterial counts. Cyclosporin A-induced suppression of anti-tularemic resistance was first noted 2-3 days following infection and remained apparent for at least 8 days. The results of these experiments demonstrate that resistance to experimental murine tularemia is mediated predominantly by a cell-mediated mechanism. This mechanism involves T cells which become activated as early as 2-3 days following infection. Experimental, non-lethal infection with Francisella tularensis is thus an excellent model for investigating the mechanisms of acquired cellular immunity.