Dei-Cas E, Brun-Pascaud M, Bille-Hansen V, Allaert A, Aliouat E M
Faculty of Medicine and Regional University Hospital Centre, Lille, France.
FEMS Immunol Med Microbiol. 1998 Sep;22(1-2):163-8. doi: 10.1111/j.1574-695X.1998.tb01201.x.
As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were essentially developed by using rats, mice, rabbits and ferrets. The rat treated with corticosteroids for 9-12 weeks is a useful PCP model. Like laboratory rats, conventional mice develop PCP after prolonged corticosteroid administration. The ferret (Mustela putorius furo) also develop PCP under corticosteroid regime. Whilst bronchoalveolar lavage (BAL) is really difficult to perform on live laboratory rodents, serial BAL sampling can be performed on live ferrets. Rabbits currently develop spontaneous PCP at weaning without corticosteroid administration. For this reason this model has been used for studying the host immune response as well as Pneumocystis-surfactant interactions. Pigs and horses also develop spontaneous PCP. Treated with corticosteroids, piglets develop extensive PCP and could be used as a non-rodent model. Pneumocystis was detected in many non-human primates. Primates could represent a source of parasites taxonomically related to P. carinii sp. f. hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis infections. Extensive PCP can be obtained within 5-7 weeks, whilst 9-12 weeks are needed in the classical model. The severe combined immunodeficiency (SCID) mouse inoculated by nasal route and the athymic nude rats intratracheally inoculated were used to test the infectivity of Pneumocystis samples coming from cultures or from different hosts. They were also used to test the anti-Pneumocystis activity of antimicrobial molecules.
由于目前仍无法获得能够从患者或其他哺乳动物宿主中分离肺孢子虫样本的体外培养系统，动物模型在肺孢子虫研究中具有至关重要的意义。该寄生虫在众多哺乳动物中均有报道，但卡氏肺孢子虫肺炎（PCP）实验模型主要是通过使用大鼠、小鼠、兔子和雪貂建立的。用皮质类固醇治疗9至12周的大鼠是一种有用的PCP模型。与实验大鼠一样，常规小鼠在长期给予皮质类固醇后也会发生PCP。雪貂（Mustela putorius furo）在皮质类固醇作用下也会发生PCP。虽然对活体实验啮齿动物进行支气管肺泡灌洗（BAL）非常困难，但可以对活体雪貂进行连续BAL采样。兔子目前在断奶时会自发发生PCP，无需给予皮质类固醇。因此，该模型已被用于研究宿主免疫反应以及肺孢子虫与表面活性剂的相互作用。猪和马也会自发发生PCP。用皮质类固醇治疗后，仔猪会发生广泛的PCP，可作为非啮齿动物模型。在许多非人灵长类动物中检测到了肺孢子虫。灵长类动物可能是与卡氏肺孢子虫人亚种分类相关的寄生虫来源。此外，灵长类动物可作为人类肺孢子虫的实验宿主。皮质类固醇治疗动物之间寄生虫水平存在明显差异，且寄生虫菌株的来源仍然未知，这是皮质类固醇治疗模型的重要缺点。出于这些原因，开发了PCP接种动物模型。在皮质类固醇治疗的非潜伏感染大鼠中气管内接种含有活寄生虫的肺匀浆，可导致广泛、可重复的肺孢子虫感染。在5至7周内即可获得广泛的PCP，而经典模型则需要9至12周。通过鼻内接种的严重联合免疫缺陷（SCID）小鼠和气管内接种的无胸腺裸大鼠被用于测试来自培养物或不同宿主的肺孢子虫样本的感染性。它们还被用于测试抗菌分子的抗肺孢子虫活性。
