Scheller L F, Wirtz R A, Azad A F
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201-1559.
Infect Immun. 1994 Nov;62(11):4844-7. doi: 10.1128/iai.62.11.4844-4847.1994.
Despite the low susceptibility of BALB/c mice to hepatic infection by Plasmodium berghei, this animal model is routinely used to investigate the basic biology of the malaria parasite and to test vaccines and the immune response against exoerythrocytic (EE) stages derived from sporozoites. A murine model in which a large number of EE parasites are established would be useful for furthering such investigations. Therefore, we assayed six mouse strains for susceptibility to erythrocytic and hepatic infections. The administration of 50 sporozoites by intravenous inoculation was sufficient to establish erythrocytic infections in five of five C57BL/6 mice compared with 10,000 sporozoites required to infect 100% of BALB/c mice. To assay for hepatic infections, mice received an intravenous inoculum of 10(6) sporozoites, and liver sections for light microscopy and histology were obtained at 29 and 44 h postinoculation. EE parasites were visualized by immunofluorescence, using an antibody to a P. falciparum heat shock protein. The mean number of EE parasites per 100 cm2 for C57BL/6 and A/J strains was significantly higher than that for BALB/c (2,190 +/- 260, 88 +/- 38, and 6 +/- 2, respectively). The proportion of inoculated sporozoites transforming into liver schizonts was 8.2% in C57BL/6 and < 1% in C3H/HeJ, DBA/1, and Swiss CD-1/ICR mice. Nonspecific inflammatory infiltrates around EE parasites were less prevalent in liver sections from C57BL/6 mice than in those from BALB/c mice, which contributed to the decrease in developing EE stages in BALB/c mice. These data indicate that the C57BL/6-P. berghei system is preferable for investigating the biology and immunology of liver stage parasites.
尽管BALB/c小鼠对伯氏疟原虫的肝脏感染敏感性较低,但该动物模型仍被常规用于研究疟原虫的基础生物学,以及测试疫苗和针对源自子孢子的红细胞外期(EE)的免疫反应。建立大量EE寄生虫的小鼠模型将有助于推进此类研究。因此,我们检测了六种小鼠品系对红细胞内和肝脏感染的易感性。通过静脉接种50个子孢子足以在五只C57BL/6小鼠中的五只中建立红细胞内感染,而感染100%的BALB/c小鼠则需要10000个子孢子。为了检测肝脏感染,小鼠接受了10⁶个子孢子的静脉接种,并在接种后29小时和44小时获取肝脏切片用于光学显微镜和组织学检查。使用抗恶性疟原虫热休克蛋白的抗体通过免疫荧光观察EE寄生虫。C57BL/6和A/J品系每100 cm²的EE寄生虫平均数量显著高于BALB/c品系(分别为2190±260、88±38和6±2)。接种的子孢子转化为肝裂殖体的比例在C57BL/6中为8.2%,在C3H/HeJ、DBA/1和瑞士CD-1/ICR小鼠中<1%。C57BL/6小鼠肝脏切片中EE寄生虫周围的非特异性炎性浸润比BALB/c小鼠的少,这导致BALB/c小鼠中发育中的EE阶段减少。这些数据表明,C57BL/6-伯氏疟原虫系统更适合用于研究肝脏期寄生虫的生物学和免疫学。