Development of Cryptosporidium parvum-induced gastrointestinal neoplasia in severe combined immunodeficiency (SCID) mice: severity of lesions is correlated with infection intensity

严重联合免疫缺陷 (SCID) 小鼠中隐孢子虫诱发的胃肠道肿瘤的发展:病变严重程度与感染强度相关

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作者:Gabriela Certad, Colette Creusy, Tramy Ngouanesavanh, Karine Guyot, Nausicaa Gantois, Anthony Mouray, Thierry Chassat, Nicolas Flament, Laurence Fleurisse, Anthony Pinon, Laurence Delhaes, Eduardo Dei-Cas

Abstract

We reported previously that Cryptosporidium parvum was able to induce intestinal tumors in severe combined immunodeficiency (SCID) mice treated with corticoids. To further characterize this Cryptosporidium-induced cell transformation, SCID mice treated with dexamethasone were challenged with C. parvum oocysts, and euthanatized sequentially after infection for histologic examination. Ki-67 was used as a marker of cellular proliferation. Our previous results were confirmed, and it was also found that mice receiving higher inocula (10(6)-10(7)) experienced more severe neoplastic development. Additionally, neoplastic changes were observed not only in the caecum but also in the stomach and duodenum of some animals. Interestingly, SCID mice (6/6) inoculated with 10(5)-10(7) oocysts showed high grade intraepithelial neoplasia or adenomas with high grade dysplasia in the caecum after Day 46 post-infection (PI). Immunohistochemistry for Ki-67 staining indicated the neoplastic process associated to cryptosporidiosis, and evidenced the first immunohistochemical alterations at early stages of the process, even at 3 weeks PI.

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