Plasmodium falciparum ookinete invasion of the midgut epithelium of Anopheles stephensi is consistent with the Time Bomb model
Plasmodium falciparum ookinete invasion of the midgut epithelium of Anopheles stephensi is consistent with the Time Bomb model
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DOI：
10.1017/s0031182004005979
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发表时间：
2004-12-01
期刊：
影响因子：
2.4
通讯作者：
Ranford-Cartwright, LC
中科院分区：
文献类型：
--
作者：
Baton, LA;Ranford-Cartwright, LC
通过膜饲养器将体外生长的恶性疟原虫配子细胞喂给实验室饲养的斯氏按蚊。在喂血后 24 至 48 小时内取出完整的中肠，包括全部血粉内容物。从中肠制备吉姆萨染色的组织学切片并通过光学显微镜检查。与之前的报道相反，动动子在中肠上皮细胞内清晰可见，表明细胞内跨中肠壁迁移。动动植物通过3个相邻细胞聚集处的侧顶膜进入上皮细胞。没有证据表明存在一组形态不同的上皮细胞，它们优先被动动物侵入。然而，动动物渗透与被侵入细胞的显着形态学变化相关，包括差异染色、细胞核浓缩和破碎、疫苗化、微绒毛丧失以及不同程度地挤出到中肠腔。在中肠腔内发现与中肠壁完全分离的上皮细胞。这些细胞与入侵的寄生虫相关，表明动动物的渗透导致入侵细胞从中肠壁完全排出。观察到形态改变的中肠细胞小簇和跨越邻近异常上皮细胞膜的入侵寄生虫，这与邻近中肠细胞之间动动子的细胞内运动一致。在未感染的中肠中也很少观察到挤出的上皮细胞。因此，上皮细胞挤出可能是组织修复的一般机制，通过该机制将受损细胞从中肠壁移除，而不是寄生虫特异性反应。这些观察结果表明，人类疟疾寄生虫对蚊子的感染与先前针对啮齿动物疟疾寄生虫提出的动动物入侵蚊子中肠上皮的定时炸弹模型是一致的，并为该模型提供了进一步的支持。
Plasmodium falciparum gametocytes grown in vitro were fed through membrane feeders to laboratory-reared Anopheles stephensi mosquitoes. Intact midguts, including entire bloodmeal contents, were removed between 24 and 48 h post-bloodfeeding. Giemsa-stained histological sections were prepared from the midguts and examined by light microscopy. Contrary to previous reports, ookinetes were clearly visible within midgut epithelial cells, demonstrating intracellular migration across the midgut wall. Ookinetes entered epithelial cells through the lateral apical membrane at sites where 3 adjacent cells converged. There was no evidence for the existence of a morphologically distinct group of epithelial cells preferentially invaded by ookinetes. However, ookinete penetration was associated with significant morphological changes to invaded cells, including differential staining, condensation and fragmentation of the nucleus, vactiolization, loss of microvilli and various degrees of extrusion into the midgut lumen. Epithelial cells completely separated from the midgut wall were found within the midgut lumen. These cells were associated with invading parasites suggesting that ookinete penetration resulted in complete ejection of invaded cells from the midgut wall. Small clusters of morphologically altered midgut cells and invading parasites spanning the membranes of adjacent abnormal epithelial cells were observed, consistent with intracellular movement of ookinetes between neighbouring midgut cells. Extruded epithelial cells were also observed rarely in uninfected midguts. Epithelial cell extrusion, therefore, may be a general mechanism of tissue repair through which damaged cells are removed from the midgut wall rather than a parasite-specific response. These observations demonstrate that human malaria parasite infection of mosquitoes is consistent with, and provides further support for, the Time Bomb model of ookinete invasion of the mosquito midgut epithelium previously proposed for rodent malaria parasites.