Cell death mechanisms are central to combat infections and to drive inflammation. The inflammasome controls infection through activation of caspase-1 leading to either IL-1β dependent inflammation, or pyroptotic cell death in infected cells. Hemolysins, which are pore-forming toxins (PFTs), alter the permeability of the host target membrane, often leading to cell death. We previously discovered a leukocidin domain-containing PFT produced by the Gram-negative bacterium Vibrio proteolyticus, named VPRH. VPRH constitutes a distinct, understudied class within the leukocidin superfamily, which is distributed among several photogenic Vibrios. Since PFTs of other pathogens were shown to activate the inflammasome pathway, we hypothesized that VPRH-induced cell death is mediated by direct activation of the inflammasome in mammalian immune host cells. Indeed, we found that VPRH induced a two-step cell death in macrophages. The first, a rapid step, was mediated by activating the NLRP3 inflammasome, leading to caspase-1 activation that resulted in IL-1β secretion and pyroptosis. The second step was independent of the inflammasome; however, its mechanism remains unknown. This study sets the foundation for better understanding the immunological consequences of inflammasome activation by a new leukocidin class of toxins, which may be shared between marine bacteria and give rise to new pathogenic isolates.

中文翻译：

---

形成弧菌的孔白蛋白通过NLRP3炎性小体激活焦细胞凋亡。

细胞死亡机制对于抵抗感染和驱动炎症至关重要。炎性小体通过激活caspase-1来控制感染，导致caspase-1依赖于IL-1β的炎症或感染细胞中的焦细胞死亡。溶血素是造孔毒素（PFT），会改变宿主靶膜的通透性，通常导致细胞死亡。我们之前发现了革兰氏阴性细菌蛋白水解弧菌产生的含白细胞介素结构域的PFT，名为VPRH。VPRH在白细胞抑素超家族中构成了一个独特的，未被研究的类别，该家族分布在几个上镜弧菌中。由于显示其他病原体的PFT激活了炎性体途径，因此我们假设VPRH诱导的细胞死亡是由哺乳动物免疫宿主细胞中的炎性体的直接激活介导的。实际上，我们发现VPRH在巨噬细胞中诱导了两步细胞死亡。第一步是快速步骤，是通过激活NLRP3炎性小体来介导的，导致caspase-1激活，从而导致IL-1β分泌和发烧。第二步独立于炎症小体。但是，其机制仍然未知。这项研究为更好地理解新的白细胞介素类毒素激活炎症小体的免疫学后果奠定了基础，该类毒素可以在海洋细菌之间共享并产生新的病原体。其机制仍然未知。这项研究为更好地理解新的白细胞介素类毒素激活炎症小体的免疫学后果奠定了基础，该类毒素可以在海洋细菌之间共享并产生新的病原体。其机制仍然未知。这项研究为更好地理解新的白细胞介素类毒素激活炎症小体的免疫学后果奠定了基础，该类毒素可以在海洋细菌之间共享并产生新的病原体。