IL-12 knockout C57BL/6 mice are protected from re-infection with Cryptosporidium parvum after challenge
IL-12 knockout C57BL/6 mice are protected from re-infection with Cryptosporidium parvum after challenge
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DOI：
10.1111/j.1550-7408.2003.tb00622.x
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发表时间：
2003-01-01
影响因子：
2.2
通讯作者：
Mead, JR
中科院分区：
文献类型：
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作者：
Ehigiator, HN;McNair, N;Mead, JR
微小隐孢子虫是一种机会性寄生原生动物，感染包括人类在内的许多哺乳动物的胃肠道。寄生虫已被确定为免疫系统受损的个体腹泻的重要原因，这与一些发病率和死亡率有关。一些研究表明，对寄生虫的免疫应答主要由细胞介导的免疫介导。IFN-γ被认为在这种免疫力的发展中起重要作用[4，11，13，14]。相反，我们实验室以前的研究表明，对C.尽管缺乏γ-干扰素，但BALB/c-Ifngtml小鼠中仍发生细小病毒（M. Smith等人，unpubl.）。从初始感染中恢复的小鼠，用10- 6个卵囊进行挑战，并且在再次感染时表现出卵囊脱落的近10倍减少。他们还表现出较短的感染期（第一次感染为25天，而第二次感染为13天）。这些数据表明BALB/c-Ifng tml小鼠产生足够的免疫力以抵抗再感染，但不产生完全的免疫力。这些小鼠中IFN-γ的缺乏表明可能存在涉及对再感染的免疫力的发展的IFN-γ非依赖性途径。与不能从感染中恢复的C57 BL/6 J-Ifng tml@小鼠相反，C57 BL/6 J-IL-12敲除小鼠产生部分γ干扰素应答并在感染后15天恢复。与BALB/c-Ifng tml@不同，在感染的IL-12敲除的脾细胞中检测到显著水平的γ干扰素，以响应特异性寄生虫抗原刺激[3]，表明Th 1是响应感染而产生的。由于这些对于持久免疫力的发展很重要，因此将该模型作为研究持久免疫效应的作用的模型进行了探索。IL-12基因敲除小鼠C. parvum提供了研究急性和继发性感染以及潜在疫苗候选物的机制。
Cryptosporidium parvum is an opportunistic parasitic protozoan that infects the gastrointestinal tracts of many mammalian species including humans. The parasite has been identified as a significant cause of diarrhea in individuals with compromised immune systems, which has been associated with some morbidity and mortality. Several studies have shown that the immune response to the parasite is primarily mediated by cell-mediated immunity. IFN-γ is believed to play a prominent role in the development of this immunity [4, 11, 13, 14]. In contrast, previous studies in our laboratory have demonstrated that development of immunity to C. parvum occurs in BALB/c-Ifng tml@ mice despite the lack of gamma interferon (M. Smith et al., unpubl.). Mice that recovered from the initial infection, were challenged with 10 6 oocysts, and demonstrated nearly a 10-fold decrease in oocyst shedding upon re-infection. They also demonstrated a shorter period of infection (25 days for the first infection compared to 13 days in the second infection). These data indicate that BALB/c-Ifng tml@ mice develop sufficient immunity to be resistant to re-infection but do not develop complete immunity. The absence of IFN-γ in these mice would suggest that there is possibly an IFN-γ-independent pathway involved the development of immunity to re-infection. These observations demonstrate the need for further study to characterize the role of the different factors that could be involved in the development of immunity to Cryptosporidium.In contrast to C57BL/6J-Ifng tml@ mice which are unable to recover from infection, C57BL/6J-IL-12 knockout mice generate a partial γ interferon response and recover by day 15 post infection. Unlike BALB/c-Ifng tml@ significant levels of γ interferon are detected in splenocytes of infected IL-12 knockouts in response to specific parasitic antigen stimulation [3], suggesting that Th1 are generated in response to infection. Since these are important for development of lasting immunity, this model was explored as a model for studying the effects of lasting immune effects. The IL-12 knockout mouse model for C. parvum offers a mechanism to study acute and secondary infections as well as potential vaccine candidates.