Caspase-1 Activation of IL-1β and IL-18 Are Essential for Shigella flexneri–Induced Inflammation

Philippe Sansonetti (1) , Armelle Phalipon (1) , Josette Arondel (1) , Kavitha Thirumalai (2) , Subhashis Banerjee (3) , Shizuo Akira (4) , Kiyoshi Takeda (4) , Arturo Zychlinsky (2)

1 Pathogénie Microbienne Moléculaire
2 Skirball Institute of Biomolecular Medicine
3 BASF Bioresearch Corporation
4 RIMD - Research Institute for Microbial Diseases [Osaka, Japan]

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)-1beta 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-1beta 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-1beta(-/-) and IL-18(-/-) mice, we show that IL-1beta 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-1beta and IL-18, in this response.

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology

Philippe Sansonetti, Armelle Phalipon, Josette Arondel, Kavitha Thirumalai, Subhashis Banerjee, et al.. Caspase-1 Activation of IL-1β and IL-18 Are Essential for Shigella flexneri–Induced Inflammation. Immunity, 2000, 12 (5), pp.581-590. ⟨10.1016/S1074-7613(00)80209-5⟩. ⟨pasteur-02875041⟩