Salmonella rapidly kill dendritic cells via a caspase-1-dependent mechanism.
Dendritic cells provide a critical link between innate and acquired immunity. In this study, we demonstrate that the bacterial pathogen Salmonella enterica serovar Typhimurium can efficiently kill these professional phagocytes via a mechanism that is dependent on sipB and the Salmonella pathogenicity island 1-encoded type III protein secretion system. Rapid phosphatidylserine redistribution, caspase activation, and loss of plasma membrane integrity were characteristic of dendritic cells infected with wild-type Salmonella, but not sipB mutant bacteria. Caspase-1 was particularly important in this process because Salmonella-induced dendritic cell death was dramatically reduced in the presence of a caspase-1-specific inhibitor. Furthermore, dendritic cells obtained from caspase-1-deficient mice, but not heterozygous littermate control mice, were resistant to Salmonella-induced cytotoxicity. We hypothesize that Salmonella have evolved the ability to selectively kill professional APCs to combat, exploit, or evade immune defense mechanisms.
van der Velden
Adrianus W M
AW
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Velasquez
Marisela
M
Starnbach
Michael N
MN
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D039521:CD11c Antigen / Q000096:biosynthesis; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D002462:Cell Membrane / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010718:Phosphatidylserines / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology
D001426:Bacterial Proteins; D039521:CD11c Antigen; D008565:Membrane Proteins; D010718:Phosphatidylserines; C440638:SPI-2 protein, Salmonella; C094579:invasion protein B, Salmonella typhimurium; D020170:Caspase 1