Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria (Nat Immunol, 2010, 11:1136-1142)

報告日期: 2011/03/29
報告時間: 16:00/16:50
報告學生: 莊詠鈞 (英文報告)
講評老師: 蔡佩珍

Full text:

Edward A Miao, et al.
Nat. Immunology 11(12): 1136-1142 (2010)
StudentYung-Chun Chuang
CommentatorDr. Pei-Jane Tsai
Time2011/03/29 3:00 P.M
PlaceRoom 602
 Macrophages play important roles in innate immunity to eliminate the pathogens or antigen presentation. During infection, intracellular pathogens could stimulate NOD-like receptors (NLRs)-induced inflammasome, which also activate caspase-1 and promote the release of proinflammatory cytokines IL-1β and IL-18. Cells which programmed cell death by this kind of mechanism called pyroptosis. Salmonella typhimurium (ST) is a lethal bacterium which does not express SPI1 or flagellin to evade caspase-1 activator NLRC4. However, ST could express another type III secretion system, SPI2, to facilitate replication in macrophages [1]. Herein, the authors used a mutant strain, ST-FliCON, which carries flagellin protein FliC by a SPI2 encoding promoter. They found NLRC4 inflammsome could activate caspase-1-induced pyroptosis which also induced IL-1β and IL-18 secretion when ST-FliCON was used. The competitive assay also showed ST-FliCON could be cleared more efficiently than wild type ST in mice. ST-FliCON-induced pyroptosis in macrophages could expose bacteria to the cytosol following by phagocytosis with neutrophils. Nevertheless, this kind of pyroptosis-induced clearance is IL-1β and IL-18 independently but relies on reactive oxygen species (ROS) in neutrophils. Taken together, this study is the first report that caspase-1-induced pyroptosis could eliminate intracellular pathogen through a ROS-dependent manner in vivo. Further study of the pyroptosis would be a new therapeutic strategy for infectious and inflammatory diseases.