Trogocytosis by Entamoeba histolytica Mediates Acquisition and Display of Human Cell Membrane Proteins and Evasion o Lysis by Human Serum
Trogocytosis by Entamoeba histolytica Mediates Acquisition and Display of Human Cell Membrane Proteins and Evasion o Lysis by Human Serum
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DOI：
10.1128/mbio.00068-19
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发表时间：
2019-03-01
期刊：
影响因子：
6.4
通讯作者：
Ralston, Katherine S.
中科院分区：
文献类型：
--
作者：
Miller, Hannah W.;Suleiman, Rene L.;Ralston, Katherine S.
我们以前表明，溶组织内阿米巴通过一种我们称为胞刺（“trogo-”意思是“蚕食”）的机制杀死人类细胞，这是因为它与其他生物体中的胞刺相似。在微生物真核生物如E.在溶组织作用中，胞刺作用用于杀死宿主细胞。在多细胞真核生物中，胞啃作用在多种情况下用于细胞杀伤和细胞间通讯。因此，蚕食是物种内部和物种之间细胞与细胞相互作用中的一个新兴主题。当哺乳动物免疫细胞之间发生胞啃时，来自被蚕食细胞的细胞膜蛋白被受体细胞获得并展示。在这项研究中，我们测试的假设，通过胞刺，阿米巴收购和展示人类细胞膜蛋白。我们证明了E. histolytica通过胞啃作用获得并展示人细胞膜蛋白，这导致保护免受人血清的裂解。只有在阿米巴原虫对活细胞进行胞噬作用而不是对死细胞进行吞噬作用后，才能对人血清产生保护作用。同样，吞噬功能缺陷但进行胞噬作用的能力不变的突变型阿米巴受人血清保护。我们的研究首次揭示了阿米巴可以展示人类细胞膜蛋白，并表明膜蛋白的获取和展示是胞啃的一般特征。这些研究对E.溶组织菌和免疫系统，也揭示了一种新的策略免疫逃避病原体。由于其他微生物真核生物利用胞刺作用杀死细胞，我们的发现可能适用于其他感染的发病机制。重要提示溶组织内阿米巴引起阿米巴病，一种潜在的致命性腹泻！疾病当阿米巴原虫能够突破肠壁并通过血流到达身体的其他部位时，可能会发生肝脏等器官的脓肿。因此，了解E.溶组织菌逃避免疫检测是非常令人感兴趣的。在这里，我们首次证明，E。histolytica通过在一个名为trogocytosis的过程中“咬”人类细胞物质来获得和展示人类细胞膜蛋白（“trogo-”意思是“啃噬”），这使得阿米巴原虫能够在人类血清中存活。先前仅在哺乳动物免疫细胞中表征了通过胞啃作用展示获得的蛋白质。我们的研究表明，这是一个更普遍的特点，并不局限于免疫细胞，并扩大了我们的知识真核生物学。这些发现还揭示了病原体免疫逃避的新策略，并可能适用于其他感染的发病机制。
We previously showed that Entamoeba histolytica kills human cells through a mechanism that we termed trogocytosis ("trogo-" means "nibble"), due to its resemblance to trogocytosis in other organisms. In microbial eukaryotes like E. histolytica, trogocytosis is used to kill host cells. In multicellular eukaryotes, trogocytosis is used for cell killing and cell-cell communication in a variety of contexts. Thus, nibbling is an emerging theme in cell-cell interactions both within and between species. When trogocytosis occurs between mammalian immune cells, cell membrane proteins from the nibbled cell are acquired and displayed by the recipient cell. In this study, we tested the hypothesis that through trogocytosis, amoebae acquire and display human cell membrane proteins. We demonstrate that E. histolytica acquires and displays human cell membrane proteins through trogocytosis and that this leads to protection from lysis by human serum. Protection from human serum occurs only after amoebae have undergone trogocytosis of live cells but not phagocytosis of dead cells. Likewise, mutant amoebae defective in phagocytosis, but unaltered in their capacity to perform trogocytosis, are protected from human serum. Our studies are the first to reveal that amoebae can display human cell membrane proteins and suggest that the acquisition and display of membrane proteins is a general feature of trogocytosis. These studies have major implications for interactions between E. histolytica and the immune system and also reveal a novel strategy for immune evasion by a pathogen. Since other microbial eukaryotes use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections.IMPORTANCE Entamoeba histolytica causes amoebiasis, a potentially fatal diarrhea! disease. Abscesses in organs such as the liver can occur when amoebae are able to breach the intestinal wall and travel through the bloodstream to other areas of the body. Therefore, understanding how E. histolytica evades immune detection is of great interest. Here, we demonstrate for the first time that E. histolytica acquires and displays human cell membrane proteins by taking "bites" of human cell material in a process named trogocytosis ("trogo-" means "nibble"), and that this allows amoebae to survive in human serum. Display of acquired proteins through trogocytosis has been previously characterized only in mammalian immune cells. Our study suggests that this is a more general feature of trogocytosis not restricted to immune cells and broadens our knowledge of eukaryotic biology. These findings also reveal a novel strategy for immune evasion by a pathogen and may apply to the pathogenesis of other infections.