National Center for Biological Sciences, Bangalore, India.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Front Cell Infect Microbiol. 2020 Jan 17;9:451. doi: 10.3389/fcimb.2019.00451. eCollection 2019.
parasites undergo a dramatic transformation during the liver stage of their life cycle, amplifying over 10,000-fold inside infected hepatocytes within a few days. Such a rapid growth requires large-scale interactions with, and manipulations of, host cell functions. Whereas hepatocyte polarity is well-known to be critical for liver function, little is presently known about its involvement during the liver stage of development. Apical domains of hepatocytes are critical components of their polarity machinery and constitute the bile canalicular network, which is central to liver function. Here, we employed high resolution 3-D imaging and advanced image analysis of -infected liver tissues to show that the parasite associates preferentially with the apical domain of hepatocytes and induces alterations in the organization of these regions, resulting in localized changes in the bile canalicular architecture in the liver tissue. Pharmacological perturbation of the bile canalicular network by modulation of AMPK activity reduces the parasite's association with bile canaliculi and arrests the parasite development. Our findings using -infected liver tissues reveal a host- interaction at the level of liver tissue organization. We demonstrate for the first time a role for bile canaliculi, a central component of the hepatocyte polarity machinery, during the liver stage of development.
寄生虫在其生命周期的肝脏阶段经历了巨大的转变，在几天内就在受感染的肝细胞内扩增了 10000 多倍。如此快速的生长需要与宿主细胞功能进行大规模的相互作用和操作。虽然众所周知，肝极性对于肝脏功能至关重要，但目前对于其在寄生虫发育的肝脏阶段中的参与情况知之甚少。肝细胞的顶端区域是其极性机制的关键组成部分，并构成了胆汁管网络，这是肝脏功能的核心。在这里，我们利用高分辨率的 3-D 成像和对 -感染的肝组织的高级图像分析，表明寄生虫优先与肝细胞的顶端区域相关联，并诱导这些区域的组织发生改变，导致肝组织中胆汁管结构的局部变化。通过调节 AMPK 活性对胆汁管网络进行药理学干扰会减少寄生虫与胆汁管的关联，并阻止寄生虫的发育。我们使用 -感染的肝组织的研究结果揭示了宿主在肝组织组织水平上的相互作用。我们首次证明了在寄生虫发育的肝脏阶段中，胆汁管作为肝细胞极性机制的核心组成部分之一发挥了作用。
