Differential roles of caspase-1 and caspase-11 in infection and inflammation.
Differential roles of caspase-1 and caspase-11 in infection and inflammation.
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DOI：
10.1038/srep45126
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发表时间：
2017-03-27
影响因子：
4.6
通讯作者：
Kanneganti TD
中科院分区：
文献类型：
--
作者：
Man SM;Karki R;Briard B;Burton A;Gingras S;Pelletier S;Kanneganti TD
Caspase-1，也称为白细胞介素-1β (IL-1β) 转换酶 (ICE)，调节抗菌宿主防御、组织修复、肿瘤发生、代谢和膜生物发生。在炎性复合体内激活后，caspase-1 会诱导细胞焦亡，并将 pro-IL-1β 和 pro-IL-18 转化为其生物活性形式。使用 129 个胚胎干细胞产生的“ICE−/−”或“Casp1−/−”小鼠在 caspase-11 位点上携带 129 相关的失活乘客突变，本质上使它们缺乏 caspase-1 和 caspase-11。如果没有额外的遗传工具，很难阐明 caspase-1 和 caspase-11 的重叠和独特功能。在这里，我们在表达 caspase-11 的 C57BL/6 J 背景上生成了 caspase-1 缺陷小鼠 (Casp1Null)。 Casp1Null 细胞不会响应 NLRC4 激活剂鼠伤寒沙门氏菌和鞭毛蛋白、经典或非经典 NLRP3 激活剂 LPS 和 ATP、大肠杆菌、啮齿类柠檬酸杆菌和 LPS 转染、AIM2 激活剂新杀弗朗西斯菌、小鼠巨细胞病毒和 DNA，以及感染因子单核细胞增多性李斯特菌和 DNA 来释放 IL-1β 和 IL-18。烟曲霉。我们进一步证明 caspase-1 和 caspase-11 对宿主防御烟曲霉感染和内毒素血症的贡献不同。
Caspase-1, also known as interleukin-1β (IL-1β)-converting enzyme (ICE), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. On activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-IL-1β and pro-IL-18 into their biologically active forms. “ICE−/−” or “Casp1−/−” mice generated using 129 embryonic stem cells carry a 129-associated inactivating passenger mutation on the caspase-11 locus, essentially making them deficient in both caspase-1 and caspase-11. The overlapping and unique functions of caspase-1 and caspase-11 are difficult to unravel without additional genetic tools. Here, we generated caspase-1–deficient mouse (Casp1Null) on the C57BL/6 J background that expressed caspase-11. Casp1Null cells did not release IL-1β and IL-18 in response to NLRC4 activators Salmonella Typhimurium and flagellin, canonical or non-canonical NLRP3 activators LPS and ATP, Escherichia coli, Citrobacter rodentium and transfection of LPS, AIM2 activators Francisella novicida, mouse cytomegalovirus and DNA, and the infectious agents Listeria monocytogenes and Aspergillus fumigatus. We further demonstrated that caspase-1 and caspase-11 differentially contributed to the host defense against A. fumigatus infection and to endotoxemia.