Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif

• Published in: Immunology Vol. 122; no. 2; pp. 222 - 229
• Main Authors: Cook, Pamela, Tötemeyer, Sabine, Stevenson, Catherine, Fitzgerald, Katherine A, Yamamoto, Masahiro, Akira, Shizuo, Maskell, Duncan J, Bryant, Clare E
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2007; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Adaptor Proteins, Vesicular Transport - immunology; Animals; bacterial infection; Bacterial Proteins - immunology; Caspase 1 - immunology; cell death; Cell Death - immunology; Cells, Cultured; Interleukin-1beta - biosynthesis; Macrophages - immunology; Macrophages - microbiology; Membrane Proteins - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; monocyte/macrophages; Original; Receptors, Interleukin - immunology; Salmonella enterica; Salmonella Infections - immunology; Salmonella typhimurium; Salmonella typhimurium - immunology; Signal Transduction - immunology; Toll-like receptor; Toll-Like Receptor 4 - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2007.02631.x

Salmonella enterica serovar typhimurium (S. typhimurium) is an intracellular pathogen that causes macrophage cell death by at least two different mechanisms. Rapid cell death is dependent on the Salmonella pathogenicity island-1 protein SipB whereas delayed cell death is independent of SipB and occurs 18-24 hr post infection. Lipopolysaccharide (LPS) is essential for the delayed cell death. LPS is the main structural component of the outer membrane of Gram-negative bacteria and is recognized by Toll-like receptor 4, signalling via the adapter proteins Mal, MyD88, Tram and Trif. Here we show that S. typhimurium induces SipB-independent cell death through Toll-like receptor 4 signalling via the adapter proteins Tram and Trif. In contrast to wild type bone marrow derived macrophages (BMDM), Tram⁻/⁻ and Trif⁻/⁻ BMDM proliferate in response to Salmonella infection.