Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA.
Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, D.C., USA.
Parasit Vectors. 2017 Dec 15;10(1):606. doi: 10.1186/s13071-017-2513-x.
Human hookworm larvae arrest development until they enter an appropriate host. This makes it difficult to access the larvae for studying larval development or host-parasite interactions. While there are in vivo and in vitro animal models of human hookworm infection, there is currently no human, in vitro model. While animal models have provided much insight into hookworm biology, there are limitations to how closely this can replicate human infection. Therefore, we have developed a human, in vitro model of the initial phase of hookworm infection using intestinal epithelial cell culture.
Co-culture of the human hookworm Ancylostoma ceylanicum with the mucus-secreting, human intestinal epithelial cell line HT-29-MTX resulted in activation of infective third-stage larvae, as measured by resumption of feeding. Larvae were maximally activated by direct contact with fully differentiated HT-29-MTX intestinal epithelial cells. HT-29-MTX cells treated with A. ceylanicum larvae showed differential gene expression of several immunity-related genes.
Co-culture with HT-29-MTX can be used to activate A. ceylanicum larvae. This provides an opportunity to study the interaction of activated larvae with the human intestinal epithelium.
人类钩虫幼虫会在进入合适宿主之前停止发育。这使得难以获取幼虫来研究幼虫发育或宿主-寄生虫相互作用。虽然有体内和体外动物模型来模拟人类钩虫感染，但目前还没有人类体外模型。虽然动物模型为钩虫生物学提供了很多深入的了解，但在多大程度上可以复制人类感染仍然存在限制。因此，我们使用肠上皮细胞培养开发了一种人类体外钩虫感染初始阶段的模型。
将人类钩虫Ancylostoma ceylanicum与分泌粘液的人肠上皮细胞系 HT-29-MTX 共同培养，通过恢复摄食来测量，结果显示感染性的第三期幼虫被激活。幼虫与完全分化的 HT-29-MTX 肠上皮细胞直接接触时被最大程度地激活。用 A. ceylanicum 幼虫处理的 HT-29-MTX 细胞显示出几种免疫相关基因的差异表达。
与 HT-29-MTX 共培养可用于激活 A. ceylanicum 幼虫。这为研究激活的幼虫与人类肠上皮细胞的相互作用提供了机会。
