Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf
Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf
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DOI：
10.1038/ni1344
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发表时间：
2006-06-01
影响因子：
30.5
通讯作者：
Aderem, Alan
中科院分区：
文献类型：
--
作者：
Miao, Edward A.;Alpuche-Aranda, Celia M.;Aderem, Alan
Macrophages respond to Salmonella typhimurium infection via Ipaf, a NACHT-leucine-rich repeat family member that activates caspase-1 and secretion of interleukin 1 beta. However, the specific microbial salmonella-derived agonist responsible for activating Ipaf is unknown. We show here that cytosolic bacterial flagellin activated caspase-1 through Ipaf but was independent of Toll-like receptor 5, a known flagellin sensor. Stimulation of the Ipaf pathway in macrophages after infection required a functional salmonella pathogenicity island 1 type III secretion system but not the flagellar type III secretion system; furthermore, Ipaf activation could be recapitulated by the introduction of purified flagellin directly into the cytoplasm. These observations raise the possibility that the salmonella pathogenicity island 1 type III secretion system cannot completely exclude 'promiscuous' secretion of flagellin and that the host capitalizes on this 'error' by activating a potent host-defense pathway.
