Group B Streptococcus induces apoptosis in macrophages

Group B Streptococcus (GBS) is a pathogen that has developed some strategie s to resist host immune defenses. Because phagocytic killing is an importan t pathogenetic mechanism for bacteria, we investigated whether GBS induces apoptosis in murine macrophages, GBS type III strain COH31 r/s (GBS-III) fi rst causes a defect in cell membrane permeability, then at 24 h, apoptosis, Apoptosis was confirmed by several techniques based on morphological chang es and DNA fragmentation. Cytochalasin D does not affect apoptosis, suggest ing that GBS;III needs not be within the macrophage cytoplasm to promote ap optosis, Inhibition of host protein synthesis prevents apoptosis, whereas i nhibition of caspase-1 or -3, does not. Therefore, GBS can trigger an apopt otic pathway independent of caspase-1 and -3, but dependent on protein synt hesist Inhibition of apoptosis by EGTA and PMA, and enhancement of apoptosi s by calphostin C and GF109203X suggests that an increase in the cytosolic calcium level and protein kinase C activity status are important in GBS-ind uced apoptosis, Neither alteration of plasma membrane permeability nor apop tosis were induced by GBS grown in conditions impeding hemolysin expression or when we used dipalmitoylphosphatidylcholine, which inhibited GBS beta-h emolytic activity, suggesting that GBS beta-hemolysin could be involved in apoptosis, beta-Hemolysin, by causing membrane permeability defects, could allow calcium influx, which initiates macrophage apoptosis, GBS also induce s apoptosis in human monocytes but not in tumor lines demonstrating the spe cificity of its activity. This study suggests that induction of macrophage apoptosis by GBS is a novel strategy to overcome host immune defenses.