Caspase-3-dependent phagocyte death during systemic Salmonella enterica serovar Typhimurium infection of mice.
Growth of Salmonella enterica in mammalian tissues results from continuous spread of bacteria to new host cells. Our previous work indicated that infective S. enterica are liberated from host cells via stochastic necrotic burst independently of intracellular bacterial numbers. Here we report that liver phagocytes can undergo apoptotic caspase-3-mediated cell death in vivo, with apoptosis being a rare event, more prevalent in heavily infected cells. The density-dependent apoptotic cell death is likely to constitute an alternative mechanism of bacterial spread as part of a bet-hedging strategy, ensuring an ongoing protective intracellular environment in which some bacteria can grow and persist.
Grant
Andrew J
AJ
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, UK. ajg60@cam.ac.uk
Sheppard
Mark
M
Deardon
Rob
R
Brown
Sam P
SP
Foster
Gemma
G
Bryant
Clare E
CE
Maskell
Duncan J
DJ
Mastroeni
Pietro
P
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3 / Q000276:immunology*; D053938:DNA Fragmentation; D005260:Female; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods; D010586:Phagocytes / Q000276:immunology* / Q000382:microbiology; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000302:isolation & purification*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D053148:Caspase 3