沙门菌感染与Caspase­-8介导的宿主细胞调控性死亡研究进展

沙门菌主要通过食物传播，严重威胁了人类健康。肠道上皮细胞作为抵抗沙门菌入侵的重要屏障，可通过多种方式抵抗沙门菌的定植与入侵。同时，肠道固有层巨噬细胞可特异性识别正常菌群与沙门菌，激活炎性小体并分泌白细胞介素(interleukin，IL)-1β等炎症因子诱导炎症反应清除沙门菌。Caspase家族属于半胱氨酸蛋白酶，它们被激活后可执行各种细胞功能。Caspase-1是炎性小体的重要组成部分，可切割消皮素D(gasdermin D)诱导细胞焦亡，引发炎症反应。研究发现，Caspase-8同样参与炎性小体复合物的形成，但其功能尚不明确。新近研究发现，在沙门菌感染所诱导的细胞焦亡被抑制时，Caspase-8在炎性小体中被强烈激活，并在肠道上皮细胞和巨噬细胞中调控细胞死亡与炎症反应，以限制沙门菌感染。因此，Caspase-8在沙门菌感染期间也是调节宿主抗感染免疫的关键分子，研究其调控宿主细胞死亡以及炎症因子释放的机制对深入了解沙门菌感染与宿主抗感染免疫应答之间的关系具有重要意义。

Advances in the study of Salmonella infection and regulated cell death of host mediating by Caspase-8

Salmonella infection which generally spread via food, is a serious threat to human health. As an important barrier against Salmonella invasion, intestinal epithelial cells reduce the colonization and invasion of Salmonella in multiple ways. At the same time, intestinal mononuclear phagocytes also recognize Salmonella through NAIP, which activates NLRC4 inflammasome to induce pyroptosis and Salmonella elimination. Caspases are a family of cysteine-aspartic proteases that carry out a variety of cellular functions. Pyroptosis mediated by Caspase-1 is the key component of inflammasomes, which induces pyroptosis by cleaving gasdermin D. Previous research found that, just like caspase-1, caspase-8 was also recruited by inflammasomes, but its function was unclear. Recent research revealed that, when pyroptosis was inhibited, Caspase-8 could be strongly activated in inflammasomes of intestinal epitheliums and macrophages which protected against Salmonella infection. Therefore, Caspase-8 can also be a key molecule to regulate host anti-infection immunity during Salmonella infection, and the mechanism of Caspase-8 in regulating host cell death is of great significance for further understanding the relationship between Salmonella infection and host anti-infection immune response.