Activation of B cell apoptotic pathways in the course of Francisella tularensis infection.
Francisella tularensis is a facultative intracellular, gram-negative bacterium that induces apoptosis in macrophages and B cells. Here we show apoptotic pathways that are activated in the Ramos human B cell line in the course of F. tularensis infection. Live bacteria F. tularensis FSC200 activate caspases 8, 9 and 3, as well as Bid; release cytochrome c and apoptosis-inducing factor from mitochondria; and induce depolarization of mitochondrial membrane potential in the Ramos cell line, thus leading these cells to apoptosis. Unlike live bacteria, killed F. tularensis FSC200 bacteria activated only caspase 3, and did not cause apoptosis of Ramos cells as measured by annexin V. Killed bacteria also caused accumulation of anti-apoptotic protein Bclx(L) in mitochondrial membranes. Thus, live F. tularensis activates both caspase pathways (receptor-mediated and intrinsic) as well as caspase-independent mitochondrial death.
Zivna
Lucie
L
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic.
Krocova
Zuzana
Z
Härtlova
Anetta
A
Kubelkova
Klara
K
Zakova
Jitka
J
Rudolf
Emil
E
Hrstka
Roman
R
Macela
Ales
A
Stulik
Jiri
J
D017209:Apoptosis; D001402:B-Lymphocytes / Q000382:microbiology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000096:biosynthesis; D053148:Caspase 3 / Q000096:biosynthesis; D053181:Caspase 8 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D005604:Francisella tularensis / Q000472:pathogenicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D045304:Cytochromes c; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9