Group BStreptococcusInduces Apoptosis in Macrophages

Abstract

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

Differing mechanisms of surviving phagosomal stress among group BStreptococcusstrains of varying genotypes

“…2A). Since GBS has been shown to induce apoptosis in macrophages, 14,15 we wanted to confirm that the difference in survival between the 2 strains was not due to increased induction of apoptosis by the ST-12 strain. Using trypan blue staining followed by viable cell counting, we found that GBS infection significantly decreases macrophage viability over time compared to the (Fig.…”

Extracellular virulence factors of group B Streptococci

“…DPPC can also inhibit GBS mediated cytokine activation (25,29), macrophage apoptosis (27) and epithelial cell invasion (25). It is interesting to speculate that a lack of DPPC inhibition of beta-h/c toxicity may in part explain the increased incidence and severity of GBS pneumonia and sepsis in premature, surfactant-deficient neonates (4).…”

“…In vitro studies confirm that the GBS beta-h/c upregulates macrophage expression of iNOS and nitric oxide (24), lung epithelial expression of IL-8 (25), and blood-brain barrier expression of a wide range of neutrophil signaling factors (e.g, IL-8, GRO-alpha, ICAM-1, GM-CSF) (26). GBS beta-h/c triggers apoptosis of macrophages in vitro, a process which is dependent on protein synthesis, but independent of caspase-1, caspase-3 or MyD88 signal tranduction pathways (27,28). Beta-h/c further promotes the ability of GBS to invade pulmonary epithelial cells, a proposed early step in the pathogenesis of systemic infection (25).…”

Septic Vs Colonizing Group B Streptococci Differentially Regulate Inflammation and Apoptosis in Human Coronary Artery Endothelial Cells - a Pilot Study

“…In addition, we could demonstrate that cleavage of Caspase 3 and Caspase 8 was increased (Figure 2). Induction of apoptosis by GBS could be previously demonstrated for macrophages, monocytes and fibroblasts, but not for other cell lines, which in consequences implicates a cell specific phenomenon [17]. It is remarkable that the septic GBS strain showed a stronger activation of Caspase 3, compared to the colonizing strain.…”

“…We assume that this stronger Caspase 3 activation is, among other factors related to the presence of ß-hemolysin, as previously demonstrated for macrophage [18] and monocyte apoptosis [19]. GBS-induced apoptosis is inhibited by the Caspase-3 inhibitor DEVD-CHO [17]. In consequence, induction of Caspase-3 might be responsible for tissue damage, leading thereby to dysregulation of hemostasis.…”