Characterization of host cell death induced by Chlamydia trachomatis.
Chlamydia are obligate intracellular bacteria that modulate apoptosis of the host cell. Strikingly, chlamydial infection has been reported both to inhibit and to induce apoptosis. Although the ability to inhibit apoptosis has been corroborated by the identification of cellular targets, confirmation of cell death induction has been complicated by a mixture of apoptotic features and atypical cell death during infection, as well as by differences in the experimental techniques used to measure cell death. Here we use a panel of well-established approaches in the study of apoptosis to define the form of cell death induced by Chlamydia trachomatis infection. Infected cells displayed apoptotic features such as nuclear condensation and fragmentation, as well as positive TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining. Fragmentation of genomic DNA occurred, but was atypical. Clear evidence against the activation of effector caspases was found. Nuclear changes were measured in fibroblasts lacking one or both of the effectors of mitochondrial apoptosis, Bax and Bak. A slight reduction in nuclear changes was observed in Bax-deficient cells and in Bax/Bak double-deficient cells. Most surprisingly, this reduction was almost complete in Bak-deficient cells. Finally, dying infected cells were efficiently taken up by professional phagocytes, suggesting that Chlamydia-induced host-cell death could play a role in the immune response. In conclusion, chlamydial infection can induce cell death. Although Chlamydia-induced cell death has certain morphological features of apoptosis, it does not result from activation of the apoptotic pathway.
Ying
Songmin
S
Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, Germany.
Fischer
Silke F
SF
Pettengill
Matthew
M
Conte
Debye
D
Paschen
Stefan A
SA
Ojcius
David M
DM
Häcker
Georg
G
D000818:Animals; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology / Q000528:radiation effects; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000472:pathogenicity; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D014466:Ultraviolet Rays; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein