Coral gasdermin triggers pyroptosis
Coral gasdermin triggers pyroptosis
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珊瑚gasdermin引发细胞焦亡
DOI：
10.1126/sciimmunol.abd2591
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发表时间：
2020-12-01
影响因子：
24.8
通讯作者：
Sun, Li
中科院分区：
文献类型：
--
作者：
Jiang, Shuai;Zhou, Zhi;Sun, Li
珊瑚气皮蛋白由半胱天冬酶3激活，参与病原体诱导的珊瑚死亡。珊瑚着火焦亡是一种炎性细胞死亡的形式，发生在病原体感染的反应中，导致细胞内内容物的释放，这些内容物是由形成孔的气皮蛋白家族蛋白介导的。Jiang等人在珊瑚中发现了一种保守的gasdermin E同源物，该同源物被珊瑚和人类caspase-3切割，形成两种活性的n端同工异构体，每一种都能诱导焦亡。在病原体感染后，造礁珊瑚poillopora damicornis中caspase依赖性气真皮蛋白E的激活与线粒体破坏和坏死有关。这些结果表明，在一些无脊椎动物中，气凝胶介导的细胞死亡可能是保守的，并且可能代表珊瑚在环境压力引起的细菌感染期间激活的免疫防御。Gasdermins是炎性细胞死亡途径的刽子手，迄今为止仅在脊椎动物中研究过。在这项研究中，我们在包括珊瑚在内的几种无脊椎动物物种中鉴定了气皮蛋白E （GSDME）的同源物。我们报道了珊瑚GSDME被caspase 3在两个位点上切割，产生了两个能够诱导焦亡的GSDME n端结构域的活性异构体。珊瑚GSDME和caspase 3在人细胞中的异位共表达促进了细胞的焦亡。珊瑚弧菌是一种引起全球珊瑚组织快速坏死的细菌病原体，感染了珊瑚后，珊瑚表现出坏死死亡，caspase 3活性升高和GSDME切割，而抑制caspase 3可阻断GSDME切割，保护珊瑚免于坏死死亡。这些结果表明，无脊椎动物中存在功能性气皮蛋白，珊瑚气皮蛋白参与了病原体诱导的珊瑚死亡。此外，我们的研究还表明，介导焦亡是一种进化上保守的功能。
Coral gasdermin is activated by caspase 3 and involved in pathogen-induced coral death. Corals catch fire Pyroptosis is a form of inflammatory cell death that occurs in response to pathogen infection and results in the release of intracellular contents mediated by the pore-forming gasdermin family proteins. Jiang et al. identified the presence of a conserved gasdermin E homolog in corals that is cleaved by both coral and human caspase-3 to form two active N-terminal isoforms each capable of inducing pyroptosis. After pathogen infection, caspase-dependent gasdermin E activation was associated with mitochondrial disruption and necrosis in the reef-building coral species Pocillopora damicornis. These results demonstrate that gasdermin-mediated cell death is likely conserved in some invertebrates and may represent an immune defense activated in corals during bacterial infection resulting from environmental stress. Gasdermins are executioners of the inflammatory cell death pathway pyroptosis that has so far been studied exclusively in vertebrates. In this study, we identified gasdermin E (GSDME) homologs in several invertebrate species including corals. We report that coral GSDME was cleaved by caspase 3 at two sites, yielding two active isoforms of GSDME N-terminal domain that were capable of inducing pyroptosis. Ectopic coexpression of coral GSDME and caspase 3 in human cells promoted pyroptosis. Corals infected with Vibrio coralliilyticus, a bacterial pathogen causing rapid tissue necrosis of corals worldwide, exhibited necrotic death with elevated caspase 3 activity and GSDME cleavage, whereas inhibition of caspase 3 blocked GSDME cleavage and protected corals from necrotic death. These results indicate that functional gasdermin exists in invertebrates and that coral gasdermin is involved in pathogen-induced coral death. Furthermore, our studies also suggest that mediation of pyroptosis is an evolutionarily conserved function of gasdermins.