TheSalmonellainvasin SipB induces macrophage apoptosis by binding to caspase-1

• DOI: 10.1073/pnas.96.5.2396
• Publication Date: 2002-07-26T14:39:15Z
• Authors: David Hersh; Denise M. Monack; Mark R. Smith; Nafisa Ghori; Stanley Falkow; Arturo Zychlinsky
• Keywords: Caspase 8; Caspase-9

Recently, Salmonella spp. were shown to induce apoptosis in infected macrophages. The mechanism responsible for this process is unknown. In report, we establish that the Inv-Spa type III secretion apparatus target invasin SipB necessary and sufficient induction of apoptosis. Purified microinjected into macrophages led cell death. Binding studies show associates with proapoptotic protease caspase-1. This interaction results activation caspase-1, as seen its proteolytic maturation processing substrate interleukin-1β. Caspase-1 activity essential cytotoxicity. Functional inhibition caspase-1 by acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone blocks macrophage cytotoxicity, lacking are not susceptible -induced Taken together, data demonstrate functions an analog Shigella IpaB.