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Caspase-1-Mediated Activation of Interleukin-1ß (IL-1ß) and IL-18 Contributes to Innate Immune Defenses against Salmonella enterica Serovar Typhimurium Infection

Department of Cellular Microbiology, Max-Planck-Institut für Infektionsbiologie, Schumannstrasse 21/22, D-10117 Berlin, Germany,¹ Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, California 94305²

Received 15 March 2006/ Returned for modification 2 May 2006/ Accepted 9 May 2006

Caspase-1 (Casp-1) mediates the processing of the proinflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 to their mature forms. Casp-1-deficient mice succumb more rapidly to Salmonella challenge than do wild-type animals. Both Casp-1 substrates, IL-18 and IL-1ß, are relevant for control of Salmonella enterica serovar Typhimurium. We used IL-18^–/– and IL-1ß^–/– mice in addition to administration of recombinant IL-18 to Casp-1^–/– mice to demonstrate that IL-18 is important for resistance to the systemic infection but not for resistance to the intestinal phase of the infection. This suggests that IL-1ß is critical for the intestinal phase of the disease. Thus, we show that Casp-1 is essential for host innate immune defense against S. enterica serovar Typhimurium and that Casp-1 substrates are required at distinct times and anatomical sites.

Editor: J. N. Weiser

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