Group B Streptococcus-Induced Macrophage Apoptosis

Abstract

Group B Streptococcus agalactiae (GBS) is a major cause of neonatal lower respiratory tract infection. Following non-opsonic phagocytosis, GBS trigger programmed cell death of macrophages, early effector cells in the lung. The elimination of macrophages may be an important strategy used by the bacteria to suppress host immune responses and to persist at sites of infection. To better understand GBS-induced programmed cell death, we evaluated mechanisms by which GBS induces apoptosis. Compared to uninfected macrophages, caspase-3 activity of GBS-infected macrophages increased 4.4 ᠲ.4 fold (p = 0.009) at 24 h and 1.7 ᠰ.7 fold at 48 h following infection and caspase-9 activity increased 1.9 ᠰ.01 fold (p = 0.009) at 48 h. GBS-infected macrophages incubated with a caspase-3 specific inhibitor had significantly increased survival compared to infected untreated macrophages. GBS also induced the release of cytochrome c from mitochondria, and depolarization of mitochondrial membrane potentials. This process was associated with increases in the pro-apoptotic protein Bad, and alterations in the regulation and localization of 14-3-3, Bcl-XL and Omi/HtrA2. We conclude GBS induces programmed cell death of macrophages by creating an imbalance in pro- and anti-apoptotic factors that ultimately activates the intrinsic pathway of apoptosis. This mechanism has not been previously associated with microbial infections.