1. Caspase-1 Activation of IL-1β and IL-18 Are Essential for Shigella flexneri–Induced Inflammation
- Author
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Josette Arondel, Philippe J. Sansonetti, Kiyoshi Takeda, Subhashis Banerjee, Kavitha Thirumalai, Arturo Zychlinsky, Armelle Phalipon, Shizuo Akira, Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Skirball Institute of Biomolecular Medicine, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), BASF Bioresearch Corporation, BASF SE, Research Institute for Microbial Diseases [Osaka, Japan] (RIMD), Osaka University [Osaka], This work was supported by a collaborative NATO grant (CLG.976285) shared by the P. J. S. and A. Z. laboratories, by a grant from the Biotechnology Program of the French Ministére de l'Education Nationale de la Recherche et la Technologie to P. J. S. and by a National Institutes of Health grant (AI37720) to A. Z., We wish to thank Michel Huerre and his group (laboratoire d'histopathologie, Institut Pasteur) for excellent assistance in histopathology and Lionel Lafitte (Service Photographie, Institut Pasteur) for assistance in image analysis., and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Proteases ,Immunology ,Caspase 1 ,Inflammation ,Shigella flexneri ,Substrate Specificity ,Microbiology ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Immunology and Allergy ,Caspase ,Dysentery, Bacillary ,0303 health sciences ,biology ,030306 microbiology ,Interleukin-18 ,Interleukin ,biology.organism_classification ,Immunohistochemistry ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,humanities ,3. Good health ,Infectious Diseases ,Apoptosis ,biology.protein ,medicine.symptom ,Interleukin-1 ,030215 immunology - Abstract
International audience; 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.
- Published
- 2000
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