期刊
IMMUNITY
卷 12, 期 5, 页码 581-590出版社
CELL PRESS
DOI: 10.1016/S1074-7613(00)80209-5
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资金
- NIAID NIH HHS [AI37720] Funding Source: Medline
Caspases are intracellular proteases that mediate mammalian cell apoptosis. Caspase-1 (Casp-1) is a unique caspase because it activates the proinflammatory cytokines interleukin (Il)-1 beta and IL-18. Shigella flexneri, the etiological agent of bacillary dysentery, induces macrophage apoptosis, which requires Casp-1 and results in the release of mature IL-1 beta and IL-18. Here we show that casp-1(-/-) mice infected with S. flexneri do not develop the acute inflammation characteristic of shigellosis and are unable to resolve the bacterial infection. Using casp-1(-/-) mice supplemented with recombinant cytokines and experiments with IL-1 beta(-/-) and IL-18(-/-) mice, we show that IL-1 beta and IL-18 are both required to mediate inflammation in S. flexneri infections. Together, these data demonstrate the importance of Casp-1 in acute inflammation and show the different roles of its substrates, IL-1 beta and IL-18, in this response.
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