The parasite Cryptosporidium invades and replicates in intestinal epithelial cells and is a leading cause of diarrheal disease and early childhood mortality. The molecular mechanisms that underlie infection and pathogenesis are largely unknown. Here, we delineate the events of host cell invasion and uncover a mechanism unique to Cryptosporidium. We developed a screen to identify parasite effectors, finding the injection of multiple parasite proteins into the host from the rhoptry organelle. These factors are targeted to diverse locations within the host cell and its interface with the parasite. One identified effector, rhoptry protein 1 (ROP1), accumulates in the terminal web of enterocytes through direct interaction with the host protein LIM domain only 7 (LMO7) an organizer of epithelial cell polarity and cell-cell adhesion. Genetic ablation of LMO7 or ROP1 in mice or parasites, respectively, impacts parasite burden in vivo in opposite ways. Taken together, these data provide molecular insight into how Cryptosporidium manipulates its intestinal host niche.

寄生虫隐孢子虫侵入并在肠上皮细胞中复制，是导致腹泻病和儿童早期死亡的主要原因。感染和发病机制的分子机制在很大程度上是未知的。在这里，我们描述了宿主细胞入侵的事件并揭示了隐孢子虫独有的机制. 我们开发了一种筛选来识别寄生虫效应器，发现多种寄生虫蛋白从菱形细胞器注入宿主。这些因素针对宿主细胞内的不同位置及其与寄生虫的界面。一种已确定的效应子，菱形蛋白 1 (ROP1)，通过与宿主蛋白 LIM 结构域仅 7 (LMO7) 直接相互作用而在肠细胞的末端网络中积累，该结构域是上皮细胞极性和细胞间粘附的组织者。小鼠或寄生虫中 LMO7 或 ROP1 的基因消融分别以相反的方式影响体内寄生虫负荷。总之，这些数据提供了关于隐孢子虫如何操纵其肠道宿主生态位的分子见解。