El Fakhry Y, Achbarou A, Desportes-Livage I, Mazier D
INSERM U313, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Paris, France.
Exp Parasitol. 1998 May;89(1):113-21. doi: 10.1006/expr.1998.4267.
IFN-gamma receptor knockout mice and wild-type mice were infected per os with Encephalitozoon intestinalis. Both groups developed an infection that was chronic in the mutant mice whereas it was only transient in wild-type mice. The infection of mutant mice was characterized by the continual shedding of spores in feces, splenomegaly, the enlargement of the biliary tract, and the occurrence of numerous nodules in the liver and in the small intestine wall. The humoral response was studied by ELISA, IFA, and Western blotting. ELISA titers of anti-E. intestinalis antibodies of IgG, IgM, and IgA isotypes were higher in IFN-gamma R0/0 mice than in wild-type mice and they increased in time after infection. Levels of IgG2a were inferior to those of IgG1 in mutant mice in contrast to wild-type mice. High levels of parasite specific antibodies were accompanied by an increase in type 2 cytokines (IL-4 and IL-10) secretion in the duodenum of IFN-gamma R0/0 mice. The E. intestinalis spore wall was recognized by IgM, IgG, and IgA from all infected mice whereas the extruded polar tube only reacted with IgG and IgA from IFN-gamma R0/0 mice after 45 days of the infection. IFN-gamma R0/0 mice IgG and IgA reacting with polar tube identified also a series of proteins which could be components of this structure. On the proteins recognized by all infected mice sera, two were first recognized by IgM at day 15 and then by IgG at day 30 in wild-type (WT) mice. The persistent reactivity of all proteins in mutant mice is consistent with the chronicity of the infection in these animals; in contrast, their resorption at day 30 in WT animals corroborates the transient character of the infection in these mice. The correlation between the evolution of the proteic pattern and the development of the infection provides evidence of the validity of this murine model to study human microsporidiosis. Indeed the reported results confirm the potential value of serological methods for diagnosing E. intestinalis infection in immunocompetent and in immunocompromised human subjects, for elucidating the age pattern of the microsporidiosis and also for identifying risk groups.
将γ干扰素受体基因敲除小鼠和野生型小鼠经口感染肠脑炎微孢子虫。两组小鼠均发生感染，突变小鼠的感染呈慢性，而野生型小鼠的感染只是短暂的。突变小鼠的感染特征为粪便中持续排出孢子、脾肿大、胆管扩张以及肝脏和小肠壁出现大量结节。通过酶联免疫吸附测定（ELISA）、间接荧光抗体试验（IFA）和蛋白质印迹法研究体液免疫反应。γ干扰素受体基因敲除小鼠中IgG、IgM和IgA同种型的抗肠脑炎微孢子虫抗体的ELISA效价比野生型小鼠高，且感染后随时间增加。与野生型小鼠相比，突变小鼠中IgG2a的水平低于IgG1。高水平的寄生虫特异性抗体伴随着γ干扰素受体基因敲除小鼠十二指肠中2型细胞因子（IL-4和IL-10）分泌增加。所有感染小鼠的IgM、IgG和IgA均可识别肠脑炎微孢子虫的孢子壁，而感染45天后，仅γ干扰素受体基因敲除小鼠的IgG和IgA与挤出的极管发生反应。与极管反应的γ干扰素受体基因敲除小鼠IgG和IgA还鉴定出一系列可能是该结构成分的蛋白质。在所有感染小鼠血清识别的蛋白质中，野生型（WT）小鼠中有两种蛋白质在第15天首先被IgM识别，然后在第30天被IgG识别。突变小鼠中所有蛋白质的持续反应性与这些动物感染的慢性特征一致；相反，WT动物在第30天这些蛋白质的消失证实了这些小鼠感染的短暂性。蛋白质模式的演变与感染发展之间的相关性为该小鼠模型用于研究人类微孢子虫病的有效性提供了证据。事实上，所报道的结果证实了血清学方法在诊断免疫功能正常和免疫功能低下的人类受试者的肠脑炎微孢子虫感染、阐明微孢子虫病的年龄模式以及识别危险人群方面的潜在价值。
