Cryptosporidium parvum infection in SCID mice infected with only one oocyst: qPCR assessment of parasite replication in tissues and development of digestive cancer.
Cryptosporidium parvum infection in SCID mice infected with only one oocyst: qPCR assessment of parasite replication in tissues and development of digestive cancer.
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DOI：
10.1371/journal.pone.0051232
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Certad G
中科院分区：
文献类型：
--
作者：
Benamrouz S;Guyot K;Gazzola S;Mouray A;Chassat T;Delaire B;Chabé M;Gosset P;Viscogliosi E;Dei-Cas E;Creusy C;Conseil V;Certad G
地塞米松(Dex)治疗的严重联合免疫缺陷(SCID)小鼠感染微小隐孢子虫后45天(P.I.)出现消化腺癌。在这个模型中，我们的目标是确定能够引起感染从而导致胃肠道肿瘤的最小卵囊数量。用含有预定剂量的校准卵囊悬浮液攻击小鼠：1、10、100或105个爱荷华州微小隐孢子虫株的卵囊。所有剂量对动物都有感染性，但增加卵囊攻击会增加小鼠的感染力(P = 0.01)。接种10个以上卵囊的小鼠在接种7天后即可观察到卵囊的脱落，攻击1个卵囊的小鼠在15天后即可观察到卵囊的脱落。在低接种量组中，与高剂量接种组相比，寄生虫生长阶段显著更高(P = 0.005)。45天后，所有组小鼠的卵囊平均排泄量均高于10,000个卵囊/克粪便。这项研究最令人印象深刻的观察是证明了微小隐孢子虫诱导的消化腺癌可能是由低剂量的隐孢子虫感染引起的，即使只有一个卵囊：在接种低剂量隐孢子虫的小鼠中，早在45d P.I.就在胃和回盲肠区域检测到肿瘤病变，这些病变可能演变为侵袭性腺癌。这些结果表明，小剂量攻击后，小鼠组织中的寄生虫有很大的扩增作用，定量PCR证实了这一点。微小隐孢子虫感染小鼠一个卵囊并发展为消化道腺癌的能力表明，包括人类在内的其他哺乳动物物种也可能对这一过程敏感，特别是当它们的免疫功能严重受损时。
Dexamethasone (Dex) treated Severe Combined Immunodeficiency (SCID) mice were previously described as developing digestive adenocarcinoma after massive infection with Cryptosporidium parvum as soon as 45 days post-infection (P.I.). We aimed to determine the minimum number of oocysts capable of inducing infection and thereby gastrointestinal tumors in this model. Mice were challenged with calibrated oocyst suspensions containing intended doses of: 1, 10, 100 or 105 oocysts of C. parvum Iowa strain. All administered doses were infective for animals but increasing the oocyst challenge lead to an increase in mice infectivity (P = 0.01). Oocyst shedding was detected at 7 days P.I. after inoculation with more than 10 oocysts, and after 15 days in mice challenged with one oocyst. In groups challenged with lower inocula, parasite growth phase was significantly higher (P = 0.005) compared to mice inoculated with higher doses. After 45 days P.I. all groups of mice had a mean of oocyst shedding superior to 10,000 oocyst/g of feces. The most impressive observation of this study was the demonstration that C. parvum-induced digestive adenocarcinoma could be caused by infection with low doses of Cryptosporidium, even with only one oocyst: in mice inoculated with low doses, neoplastic lesions were detected as early as 45 days P.I. both in the stomach and ileo-caecal region, and these lesions could evolve in an invasive adenocarcinoma. These findings show a great amplification effect of parasites in mouse tissues after challenge with low doses as confirmed by quantitative PCR. The ability of C. parvum to infect mice with one oocyst and to develop digestive adenocarcinoma suggests that other mammalian species including humans could be also susceptible to this process, especially when they are severely immunocompromised.
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