Boylan C J, Current W L
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Infect Immun. 1992 Apr;60(4):1589-97. doi: 10.1128/iai.60.4.1589-1597.1992.
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.
描述了一种卡氏肺孢子虫肺炎的免疫抑制大鼠模型，该模型利用简单、无创的气管内接种冷冻保存的寄生虫，在5周内导致严重的卡氏肺孢子虫肺炎。这是对最常用的卡氏肺孢子虫肺炎模型的改进，后者依赖免疫抑制来激活潜伏的卡氏肺孢子虫感染，通常需要8至12周才能产生严重的卡氏肺孢子虫感染。它也比最近需要手术接种寄生虫的模型劳动强度小。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、卡氏肺孢子虫接种和卡氏肺孢子虫实验室保存的合适方法；并确定有效的动物饲养方法，以保持动物免受严重的继发感染。我们更详细研究的结果表明，接受两到三次气管内接种约10(6)个冷冻保存的卡氏肺孢子虫生物体的动物有可预测的疾病进展过程，包括3周内中度卡氏肺孢子虫感染、5周内严重卡氏肺孢子虫肺炎以及6周内由于卡氏肺孢子虫肺炎导致的高死亡率。无论接种的卡氏肺孢子虫数量多少，寄生虫在左右肺之间均匀分布。饲养在微型隔离笼中的未接种卡氏肺孢子虫的免疫抑制对照大鼠未感染卡氏肺孢子虫，从而提供了许多卡氏肺孢子虫肺炎模型中缺少的重要对照。大多数未接种卡氏肺孢子虫的对照动物和用甲氧苄啶-磺胺甲恶唑治疗的接种卡氏肺孢子虫的大鼠，饲养在与重度感染动物同一房间的开放笼中，在免疫抑制5至6周后没有可检测到的感染；然而，一些动物肺部有少量卡氏肺孢子虫。由于气管内接种5周后可实现重度、可重复的感染，由于很少有动物因继发感染而死亡，并且由于动物可以作为未感染的同期对照进行饲养，该动物模型可用于卡氏肺孢子虫菌株的保存、卡氏肺孢子虫传播和自然史的研究、为实验室研究生产大量生物体以及评估潜在的抗卡氏肺孢子虫药物。
