Listeriolysin O from Listeria monocytogenes is a lymphocyte apoptogenic molecule.
Infection of mice with Listeria monocytogenes caused marked lymphocyte apoptosis in the white pulp of the spleen on day 2 postinfection. We prove in this study that listeriolysin O (LLO), a pore-forming molecule and a major virulence factor of Listeria, could directly induce murine lymphocyte apoptosis both in vivo and in vitro at nanomolar and subnanomolar doses. Induction of apoptosis by LLO was rapid, with caspase activation seen as early as 30 min post-treatment. T cells lost their mitochondrial membrane potential and exposed phosphatidylserine within 8 h of treatment. Incubation of lymphocytes with a pan-caspase inhibitor blocked DNA laddering and caspase-3 activation, but did not block phosphatidylserine exposure or loss of mitochondrial membrane potential. We describe a novel function for LLO: induction of lymphocyte apoptosis with rapid kinetics, effected by both caspase-dependent and -independent pathways.
Carrero
Javier A
JA
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Calderon
Boris
B
Unanue
Emil R
ER
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000633:toxicity*; D006460:Hemolysin Proteins; D007279:Injections, Subcutaneous; D007425:Intracellular Membranes / Q000382:microbiology / Q000473:pathology; D008089:Listeria monocytogenes / Q000276:immunology*; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D008564:Membrane Potentials / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008928:Mitochondria / Q000382:microbiology / Q000473:pathology; D010539:Permeability; D010718:Phosphatidylserines / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D010718:Phosphatidylserines; D020169:Caspases; C038705:hlyA protein, Listeria monocytogenes