Cryptosporidium parvum, a potential cause of colic adenocarcinoma.
Cryptosporidium parvum, a potential cause of colic adenocarcinoma.
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DOI：
10.1186/1750-9378-2-22
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发表时间：
2007-11-21
影响因子：
3.7
通讯作者：
Creusy, Colette
中科院分区：
文献类型：
--
作者：
Certad, Gabriela;Ngouanesavanh, Tramy;Creusy, Colette
背景：隐孢子虫病是一个重大的公共卫生问题。这种感染在世界范围内被报告为腹泻的常见原因。特别是，在免疫功能低下的患者中，它仍然是一种临床上意义重大的机会性感染，在艾滋病毒感染者中导致潜在威胁生命的腹泻。然而，对这种感染的不同方面，如侵袭、传播和发病机制的理解是有问题的。此外，很难找到合适的动物模型来繁殖这种寄生虫。需要努力建立可复制的动物模型，既允许不同物种的常规传代，又可以接近隐孢子虫感染的未知方面，特别是在病理生理学领域。结果：我们建立了一种成年严重联合免疫缺陷(SCID)小鼠接种微小隐孢子虫或小鼠隐孢子虫的动物模型，并在地塞米松(Dex)治疗或不治疗的情况下，研究了在开放前期、卵囊脱落或临床和组织病理学表现方面的差异。无论处于何种化学免疫抑制状态，感染小鼠的卵囊的排泄量都很高。地塞米松治疗和未治疗的小鼠平均潜伏期分别为11天和9.7天。两组寄生虫感染均局限于胃部，且对胃底区有明显的优势定植。在感染细小球虫的小鼠中，地塞米松治疗的SCID小鼠成为慢性脱落者，平均潜伏期为6.2天。接种地塞米松的小鼠出现腺囊性息肉，伴有上皮内肿瘤和粘膜内腺癌的存在。结论：首次发现微小隐孢子虫与地塞米松治疗的SCID小鼠肠道息肉和腺癌的形成有关。此外，我们还开发了一种模型，用皮质激素治疗的SCID小鼠比较慢性小鼠隐孢子虫病和微小隐孢子虫病。这种可复制的模型有助于评估临床症状、卵囊脱落、感染位置、致病性和胃肠道组织病理学变化，表明根据引起感染的隐孢子虫种类，地塞米松的作用不同。
BACKGROUND: Cryptosporidiosis represents a major public health problem. This infection has been reported worldwide as a frequent cause of diarrhoea. Particularly, it remains a clinically significant opportunistic infection among immunocompromised patients, causing potentially life-threatening diarrhoea in HIV-infected persons. However, the understanding about different aspects of this infection such as invasion, transmission and pathogenesis is problematic. Additionally, it has been difficult to find suitable animal models for propagation of this parasite. Efforts are needed to develop reproducible animal models allowing both the routine passage of different species and approaching unclear aspects of Cryptosporidium infection, especially in the pathophysiology field.RESULTS: We developed a model using adult severe combined immunodeficiency (SCID) mice inoculated with Cryptosporidium parvum or Cryptosporidium muris while treated or not with Dexamethasone (Dex) in order to investigate divergences in prepatent period, oocyst shedding or clinical and histopathological manifestations. C. muris-infected mice showed high levels of oocysts excretion, whatever the chemical immunosuppression status. Pre-patent periods were 11 days and 9.7 days in average in Dex treated and untreated mice, respectively. Parasite infection was restricted to the stomach, and had a clear preferential colonization for fundic area in both groups. Among C. parvum-infected mice, Dex-treated SCID mice became chronic shedders with a prepatent period of 6.2 days in average. C. parvum-inoculated mice treated with Dex developed glandular cystic polyps with areas of intraepithelial neoplasia, and also with the presence of intramucosal adenocarcinoma.CONCLUSION: For the first time C. parvum is associated with the formation of polyps and adenocarcinoma lesions in the gut of Dex-treated SCID mice. Additionally, we have developed a model to compare chronic muris and parvum cryptosporidiosis using SCID mice treated with corticoids. This reproducible model has facilitated the evaluation of clinical signs, oocyst shedding, location of the infection, pathogenicity, and histopathological changes in the gastrointestinal tract, indicating divergent effects of Dex according to Cryptosporidium species causing infection.