Inflammasomes are innate immune mechanisms that activate caspase-1 in response to a variety of stimuli, including Salmonella infection. Active caspase-1 has a potential to induce two different types of cell death, depending on the expression of the pyroptosis mediator gasdermin D (GSDMD); following caspase-1 activation, GSDMD-sufficient and GSDMD-null/low cells undergo pyroptosis and apoptosis, respectively. Although Bid, a caspase-1 substrate, plays a critical role in caspase-1 induction of apoptosis in GSDMD-null/low cells, an additional mechanism that mediates this cell death independently of Bid has also been suggested. This study investigated the Bid-independent pathway of caspase-1-induced apoptosis. Caspase-1 has been reported to process caspase-6 and caspase-7. Silencing of caspase-7, but not caspase-6, significantly reduced the activation of caspase-3 induced by caspase-1, which was activated by chemical dimerization, in GSDMD/Bid-deficient cells. CRISPR/Cas9-mediated depletion of caspase-7 had the same effect on the caspase-3 activation. Moreover, in the absence of GSDMD and Bid, caspase-7 depletion reduced apoptosis induced by caspase-1 activation. Caspase-7 was activated following caspase-1 activation independently of caspase-3, suggesting that caspase-7 acts downstream of caspase-1 and upstream of caspase-3. Salmonella induced the activation of caspase-3 in GSDMD-deficient macrophages, which relied partly on Bid and largely on caspase-1. The caspase-3 activation and apoptotic morphological changes seen in Salmonella-infected GSDMD/Bid-deficient macrophages were attenuated by caspase-7 knockdown. These results suggest that in addition to Bid, caspase-7 can also mediate caspase-1-induced apoptosis and provide mechanistic insights into inflammasome-associated cell death that is one major effector mechanism of inflammasomes.

中文翻译：

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Caspase-7独立于Bid介导caspase-1诱导的凋亡。

炎性小体是先天免疫机制，可响应各种刺激（包括沙门氏菌感染）激活caspase-1。活跃的caspase-1可能会诱导两种不同类型的细胞死亡，具体取决于焦磷酸化介导的胃泌素D（GSDMD）的表达。在caspase-1激活后，充足的GSDMD细胞和GSDMD无效/低细胞分别发生凋亡和凋亡。尽管Bid（一种caspase-1底物）在caspase-1诱导GSDMD空/低细胞凋亡中起关键作用，但也有人提出了独立于Bid介导此细胞死亡的其他机制。这项研究调查了caspase-1诱导的凋亡的独立于出价的途径。据报道，caspase-1处理caspase-6和caspase-7。沉默caspase-7，而不沉默caspase-6，在GSDMD / Bid缺陷细胞中，Caspase-1诱导的caspase-3激活显着降低，而caspase-1诱导的caspase-3激活是由化学二聚作用激活的。CRISPR / Cas9介导的caspase-7耗竭对caspase-3激活具有相同的作用。此外，在没有GSDMD和Bid的情况下，caspase-7耗竭减少了caspase-1激活诱导的凋亡。caspase-1激活后，caspase-7被激活，独立于caspase-3，这表明caspase-7在caspase-1下游和caspase-3上游起作用。沙门氏菌诱导了GSDMD缺陷型巨噬细胞中caspase-3的活化，这部分依赖于Bid，主要依赖于caspase-1。caspase-7敲低减弱了沙门氏菌感染的GSDMD / Bid缺陷型巨噬细胞中caspase-3的激活和凋亡形态学改变。这些结果表明，除了出价之外，