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Improved rat model of Pneumocystis carinii pneumonia: induced laboratory infections in Pneumocystis-free animals.

机译:卡氏肺孢子虫肺炎的改良大鼠模型:无肺孢菌的动物诱发实验室感染。

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An immunosuppressed rat model of Pneumocystis carinii pneumonia is described that utilizes simple, noninvasive intratracheal (i.t.) inoculation of cryopreserved parasites and results in development of severe P. carinii pneumonia within 5 weeks. This is an improvement over the most commonly used models of P. carinii pneumonia that rely on immune suppression to activate latent P. carinii infections and that often require 8 to 12 weeks to produce heavy infections of P. carinii. It is also less labor intensive than more recent models requiring surgical instillation of parasites. Our report describes a series of preliminary studies to select an appropriate strain of rat; to determine suitable methods for inducing uniform immunosuppression, P. carinii inoculation, and laboratory maintenance of P. carinii; and to determine effective animal husbandry methods for maintaining animals free from serious secondary infections. Results of our more detailed studies demonstrate that animals receiving two or three i.t. inoculations of approximately 10(6) cryopreserved P. carinii organisms have a predictable course of disease progression which includes moderate P. carinii infections within 3 weeks, severe P. carinii pneumonia in 5 weeks, and a high percentage of mortality due to P. carinii pneumonia in 6 weeks. Parasites were distributed evenly between the right and left lungs, regardless of the number of P. carinii inoculations administered. Non-P. carinii-inoculated immunosuppressed control rats maintained in microisolator cages remained free of P. carinii, thus providing an important control that is missing from many P. carinii pneumonia models. Most non-P. carinii-inoculated control animals and P. carinii-inoculated rats treated with trimethoprim-sulfamethoxazole that were housed in open caging in the same room containing heavily infected animals had no detectable infections after 5 to 6 weeks of immunosuppression; however, some had a small number of P. carinii in their lungs. Because heavy, reproducible infections are achieved 5 weeks after i.t. inoculation, because few animals are lost to secondary infections, and because animals can be maintained as noninfected contemporaneous controls, this animal model is useful for the maintenance of P. carinii strains, for studies of the transmission and natural history of P. carinii, for the production of large numbers of organisms for laboratory studies, and for the evaluation of potential anti-P. carinii drugs.
机译:描述了一种免疫抑制的卡氏肺孢子虫肺炎大鼠模型,该模型利用简单,无创的气管内(i.t.)接种冷冻保存的寄生虫,并在5周内导致严重的卡氏肺孢子虫肺炎的发展。这是对最常用的卡那氏肺炎模型的一种改进,该模型依靠免疫抑制来激活潜伏的卡氏肺炎感染,并且通常需要8到12周才能产生卡氏疟原虫的重度感染。与需要通过手术灌输寄生虫的最新模型相比,它的劳动强度更低。我们的报告描述了一系列初步研究,以选择合适的大鼠品系。确定诱导均匀免疫抑制,卡氏疟原虫接种和实验室维护卡氏疟原虫的合适方法;并确定有效的畜牧方法,以使动物免受严重的继发感染。我们更详细的研究结果表明,动物接受了两次或三个腹腔注射。接种约10(6)个冷冻保存的卡氏疟原虫微生物具有可预测的疾病进展过程,包括3周内出现中等程度的卡氏疟原虫感染,5周内出现严重的卡氏疟原虫肺炎,以及因卡氏疟原虫而导致的高死亡率6周内出现肺炎。不论所接种的卡氏疟原虫接种数量如何,寄生虫均在左右肺之间均匀分布。非P。维持在微隔离笼中的卡林氏菌接种的免疫抑制的对照大鼠保持无卡氏疟原虫,因此提供了许多卡氏疟原虫肺炎模型所缺少的重要对照。大多数非P。免疫抑制5至6周后,在装有严重感染动物的同一个房间内,在开放的笼中饲养了用甲氧苄氨嘧啶-磺胺甲基异恶唑处理过的卡里氏菌接种的对照动物和卡那氏菌接种的大鼠。但是,有些人的肺中有少量卡氏疟原虫。因为在i.t.手术后5周即可达到重度,可重现的感染。接种,因为很少有动物因继发感染而丧生,并且由于可以将动物作为未感染的同期对照进行饲养,因此该动物模型可用于维持卡氏疟原虫菌株,用于研究卡氏疟原虫的传播和自然史,用于实验室研究以及评估潜在抗P的大量生物的生产。卡里尼药物。

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