Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis
Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis
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DOI：
10.1073/pnas.0802773105
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发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Orth, Kim
中科院分区：
文献类型：
--
作者：
Burdette, Dara L.;Yarbrough, Melanie L.;Orth, Kim
细菌病原体副溶血弧菌利用 III 型分泌系统在感染后数小时内导致宿主细胞死亡。我们报告说，细胞死亡完全独立于细胞凋亡，并且通过注射多种 III 型效应物引起自噬诱导、细胞变圆以及随后细胞内容物释放的机制发生。通过脂化轻链 3 (LC3) 的出现以及点和液泡形成的增加来检测自噬。电子显微镜揭示了感染过程中早期自噬囊泡的产生。与磷酸肌醇 3 (PI3) 激酶在自噬中发挥作用相一致，用 PI3 激酶抑制剂处理受感染的细胞会减弱受感染细胞的自噬。由于副溶血性弧菌感染期间会注射许多效应器，因此单一 PI3 激酶抑制剂的存在不能阻止不可避免的宿主细胞死亡也就不足为奇了。我们的研究揭示了一种感染模式，其中细胞外病原体利用其 III 型分泌系统引起至少三个平行事件，最终导致受感染宿主细胞的促炎性死亡。
The bacterial pathogen Vibrio parahaemolyticus utilizes a type III secretion system to cause death of host cells within hours of infection. We report that cell death is completely independent of apoptosis and occurs by a mechanism in which injection of multiple type III effectors causes induction of autophagy, cell rounding, and the subsequent release of cellular contents. Autophagy is detected by the appearance of lipidated light chain 3 (LC3) and by increases in punctae and vacuole formation. Electron microscopy reveals the production of early autophagic vesicles during infection. Consistent with phosphoinositide 3 (PI3) kinase playing a role in autophagy, treatment of infected cells with a PI3 kinase inhibitor attenuates autophagy in infected cells. Because many effectors are injected during a V. parahaemolytkus infection, it is not surprising that the presence of a sole PI3 kinase inhibitor does not prevent inevitable host-cell death. Our studies reveal an infection paradigm whereby an extracellular pathogen uses its type III secretion system to cause at least three parallel events that eventually result in the proinflammatory death of an infected host cell.