Garza Armandina, Castellanos-Gonzalez Alejandro, Griffiths Jeffrey, Robinson Prema
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, One Baylor Plaza, Rm 535EA, Houston, TX 77030, USA.
Parasitol Res. 2008 Feb;102(3):457-63. doi: 10.1007/s00436-007-0785-3. Epub 2007 Nov 28.
Cryptosporidiosis, caused by Cryptosporidium, causes self-limited diarrhea in normal hosts but may cause life-threatening diarrhea in immunocompromised persons. Cryptosporidium-induced manifestations, including weight-loss and intestinal physiological alterations are not noted in adult immunocompetent mice. So far, studies that have been used to test the therapeutic efficacy of drugs have been performed using various immunocompromised animal models. There is an urgent need of an immunocompetent small animal model that portrays Cryptosporidium-induced manifestations. In the current studies, we have compared two Cryptosporidium parvum pretreatment methods, we have hence used sodium hypochlorite or acidic water to treat Cryptosporidium parvum, followed by infection by oral gavage in adult immunocompetent C57BL6 mice. We demonstrated manifestations such as weight loss, intestinal structural and physiological alterations such as intestinal, villi blunting, and glucose malabsorption (as studied by the Ussing chamber technique) only in response to infection with C. parvum that has been treated with acidic water and not with sodium hypochlorite. These novel studies reveal that acidic water treatment of C. parvum results in manifestations of cryptosporidiosis in otherwise resistant immunocompetent mice. The current studies open up possibilities of using the normal immunocompetent mice model to test therapeutic drugs against cryptosporidiosis.
由隐孢子虫引起的隐孢子虫病在正常宿主中会导致自限性腹泻,但在免疫功能低下的人群中可能会导致危及生命的腹泻。在成年免疫功能正常的小鼠中未观察到隐孢子虫引起的包括体重减轻和肠道生理改变在内的表现。到目前为止,用于测试药物治疗效果的研究都是使用各种免疫功能低下的动物模型进行的。迫切需要一种能呈现隐孢子虫引起的表现的免疫功能正常的小动物模型。在当前的研究中,我们比较了两种微小隐孢子虫预处理方法,因此我们使用次氯酸钠或酸性水来处理微小隐孢子虫,然后通过口服灌胃感染成年免疫功能正常的C57BL6小鼠。我们仅在感染经酸性水处理而非次氯酸钠处理的微小隐孢子虫时才观察到体重减轻、肠道结构和生理改变,如肠绒毛变钝和葡萄糖吸收不良(通过尤斯灌流小室技术研究)等表现。这些新的研究表明,对微小隐孢子虫进行酸性水处理会在原本具有抵抗力的免疫功能正常的小鼠中引发隐孢子虫病的表现。当前的研究为使用正常免疫功能正常的小鼠模型来测试抗隐孢子虫病的治疗药物开辟了可能性。