Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif.
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.
Cook
Pamela
P
Centre for Veterinary Science, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Tötemeyer
Sabine
S
Stevenson
Catherine
C
Fitzgerald
Katherine A
KA
Yamamoto
Masahiro
M
Akira
Shizuo
S
Maskell
Duncan J
DJ
Bryant
Clare E
CE
D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology*; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D020170:Caspase 1 / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*
D033942:Adaptor Proteins, Vesicular Transport; D001426:Bacterial Proteins; D020170:Caspase 1; D053583:Interleukin-1beta; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D051197:Toll-Like Receptor 4; C476286:Ticam1 protein, mouse; C476416:Ticam2 protein, mouse; C493487:Tlr4 protein, mouse; C094579:invasion protein B, Salmonella typhimurium