Role of Bcl-2 family members in caspase-independent apoptosis during Chlamydia infection.
Infection with an obligate intracellular bacterium, the Chlamydia trachomatis lymphogranuloma venereum (LGV/L2) strain or the guinea pig inclusion conjunctivitis serovar of Chlamydia psittaci, leads to apoptosis of host cells. The apoptosis is not affected by a broad-spectrum caspase inhibitor, and caspase-3 is not activated in infected cells, suggesting that apoptosis mediated by these two strains of Chlamydia is independent of known caspases. Overexpression of the proapoptotic Bcl-2 family member, Bax, was previously shown to induce caspase-independent apoptosis, and we find that Bax is activated and translocates from the cytosol to the mitochondria in C. psittaci-infected cells. C. psittaci-induced apoptosis is inhibited in host cells overexpressing Bax inhibitor-1 and is inhibited through overexpression of Bcl-2, which blocks both caspase-dependent and -independent apoptosis. As Bax and mitochondria are ideally located to sense stress-related metabolic changes emanating from the interior of an infected cell, it is likely that Bax-dependent apoptosis may also be observed in cells infected with other intracellular pathogens.
Perfettini
Jean-Luc
JL
Unité de Biologie Moléculaire du Gène, INSERM U.277, Université Paris 7, France.
Reed
John C
JC
Israël
Nicole
N
Martinou
Jean-Claude
JC
Dautry-Varsat
Alice
A
Ojcius
David M
DM
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D002692:Chlamydia trachomatis / Q000502:physiology*; D002691:Chlamydophila psittaci / Q000502:physiology*; D003235:Conjunctivitis, Inclusion / Q000382:microbiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008219:Lymphogranuloma Venereum / Q000382:microbiology; D008565:Membrane Proteins / Q000096:biosynthesis; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020298:U937 Cells; D051028:bcl-2-Associated X Protein
D000590:Amino Acid Chloromethyl Ketones; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C484209:TMBIM6 protein, human; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone