Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection.
Caspase-1 (Casp-1) mediates the processing of the proinflammatory cytokines interleukin-1beta (IL-1beta) 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-1beta, are relevant for control of Salmonella enterica serovar Typhimurium. We used IL-18-/- and IL-1beta-/- 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-1beta 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.
Raupach
Bärbel
B
Department of Cellular Microbiology, Max-Planck-Institut für Infektionsbiologie, Schumannstrasse 21/22, 10117 Berlin, Germany.
Peuschel
Soo-Kyung
SK
Monack
Denise M
DM
Zychlinsky
Arturo
A
D000818:Animals; D020170:Caspase 1 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D020382:Interleukin-18 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity*; D013047:Specific Pathogen-Free Organisms
D007375:Interleukin-1; D020382:Interleukin-18; D020170:Caspase 1