Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome
Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome
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DOI：
10.1038/ni.2222
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发表时间：
2012-03-01
影响因子：
30.5
通讯作者：
Geijtenbeek, Teunis B. H.
中科院分区：
文献类型：
--
作者：
Gringhuis, Sonja I.;Kaptein, Tanja M.;Geijtenbeek, Teunis B. H.
树突状细胞产生促炎细胞因子白细胞介素1 β（IL-1 β）在宿主防御中至关重要。在这里，我们确定了一个以前未知的作用dectin-1在激活一个非经典的半胱天冬酶-8炎症反应的真菌和分枝杆菌。Dectin-1通过激酶Syk介导的信号传导途径诱导IL-1 β的产生和成熟。尽管CARD 9-Bcl-10-MALT 1支架指导IL 1B转录，但MALT 1-胱天蛋白酶-8和ASC募集到该支架中对于胱天蛋白酶-8加工pro-IL-1 β至关重要。与典型的caspase-1炎性体的激活相反，其需要额外的胞质受体的激活，非典型的caspase-8炎性体的激活不依赖于病原体的内化。因此，dectin-1作为病原体的细胞外传感器，通过非经典的半胱天冬酶-8依赖性炎性小体诱导IL-1 β的产生和成熟，用于保护性免疫。
Production of the proinflammatory cytokine interleukin 1 beta (IL-1 beta) by dendritic cells is crucial in host defense. Here we identify a previously unknown role for dectin-1 in the activation of a noncanonical caspase-8 inflammasome in response to fungi and mycobacteria. Dectin-1 induced both the production and maturation of IL-1 beta through signaling routes mediated by the kinase Syk. Whereas the CARD9-Bcl-10-MALT1 scaffold directed IL1B transcription, the recruitment of MALT1-caspase-8 and ASC into this scaffold was crucial for processing of pro-IL-1 beta by caspase-8. In contrast to activation of the canonical caspase-1 inflammasome, which requires additional activation of cytosolic receptors, activation of the noncanonical caspase-8 inflammasome was independent of pathogen internalization. Thus, dectin-1 acted as an extracellular sensor for pathogens that induced both IL-1 beta production and maturation through a noncanonical caspase-8-dependent inflammasome for protective immunity.