CLEC7A/炎症小体通路
中文名称
通路描述
通过诱导 Th17 细胞反应来介导抗真菌免疫需要产生成熟、活化的白细胞介素 -1β（IL1B）。CLEC7A（dectin-1）通过 SYK 途径诱导 NF-κB 激活，并转录编码 pro-IL1B 的基因，通过 CARD9-BCL10-MALT1 复合物以及 MALT1-caspase-8-ASC 复合物的形成和激活，介导 pro-IL1B 的切割。无活性的前体 pro-IL1B 必须被加工为成熟的生物活性 IL1B 形式，通常由炎症半胱氨酸蛋白酶 caspase-1 介导。Gringhuis 等人显示，CLEC7A 介导的 IL1B 加工通过两种不同的机制发生：CLEC7A 触发了非经典 caspase-8 炎症小体以介导 pro-IL1B 加工，该过程独立于 caspase-1 活性，而某些真菌触发了第二种额外的机制，需要激活 NLRP3/caspase 1 炎症小体。与经典 caspase-1 炎症小体不同，CLEC7A 介导的非经典 caspase-8 依赖性炎症小体独立于病原体内吞。CLEC7A/炎症小体通路使宿主免疫系统能够针对真菌和细菌感染发起保护性的 Th17 反应（Gringhuis et al. 2012, Cheng et al. 2011）。
英文描述
CLEC7A/inflammasome pathway Antifungal immunity through the induction of T-helper 17 cells (TH17) responses requires the production of mature, active interleukin-1beta (IL1B). CLEC7A (dectin-1) through the SYK route induces activation of NF-kB and transcription of the gene encoding pro-IL1B via the CARD9-BCL10-MALT1 complex as well as the formation and activation of a MALT1-caspase-8-ASC complex that mediated the processing of pro-IL1B. The inactive precursor pro-IL1B has to be processed into mature bioactive form of IL1B and is usually mediated by inflammatory cysteine protease caspase-1. Gringhuis et al. showed that CLEC7A mediated processing of IL1B occurs through two distinct mechanisms: CLEC7A triggering induced a primary noncanonical caspase-8 inflammasome for pro-IL1B processing that was independent of caspase-1 activity, whereas some fungi triggered a second additional mechanism that required activation of the NLRP3/caspase 1 inflammasome. Unlike the canonical caspase-1 inflammasome, CLEC7A mediated noncanonical caspase-8-dependent inflammasome is independent of pathogen internalization. CLEC7A/inflammasome pathway enables the host immune system to mount a protective TH17 response against fungi and bacterial infection (Gringhuis et al. 2012, Cheng et al. 2011).
所含基因
6 个基因