Mechanisms of group B streptococcal-induced apoptosis of murine macrophages.
Apoptosis of murine and human macrophages induced by group B Streptococcus agalactiae (GBS) is likely an important virulence mechanism that is used by the bacteria to suppress the host immune response and to persist at sites of infection. The mechanisms by which GBS induces apoptosis are, however, largely unknown. In this study, we report that in murine macrophages GBS induces unique changes in the regulation and localization of the apoptotic regulators Bad, 14-3-3, and Omi/high-temperature requirement A2 and leads to the release of cytochrome c and the activation of caspase-9 and caspase-3. Furthermore, inhibition of caspase-3 impaired GBS-induced apoptosis of macrophages. The ability to modulate the activity of effector caspases may therefore represent an unexploited avenue for therapeutic intervention in GBS infections.
Ulett
Glen C
GC
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Maclean
Kirsteen H
KH
Nekkalapu
Sunitha
S
Cleveland
John L
JL
Adderson
Elisabeth E
EE
D048948:14-3-3 Proteins / Q000378:metabolism / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D000074923:High-Temperature Requirement A Serine Peptidase 2; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D024101:Mitochondrial Proteins; D012697:Serine Endopeptidases / Q000378:metabolism / Q000502:physiology; D013292:Streptococcus agalactiae / Q000276:immunology*; D051025:bcl-Associated Death Protein / Q000378:metabolism / Q000502:physiology
D048948:14-3-3 Proteins; D061945:Caspase Inhibitors; D024101:Mitochondrial Proteins; D051025:bcl-Associated Death Protein; D045304:Cytochromes c; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; C000615915:Htra2 protein, mouse; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases