Fas (CD95)-Fas ligand interactions are responsible for monocyte apoptosis occurring as a result of phagocytosis and killing of Staphylococcus aureus

Human peripheral blood monocytes become apoptotic following phagocytosis of Staphylococcus aureus. In this study, we investigated the mechanisms invol ved in this phenomenon. Cells exposed to bacteria were examined for the sur face expression of Fas and Fas ligand (FasL). The level of soluble form of FasL was also measured in the culture supernatants. As Fas-mediated apoptos is involves the activation of caspases, the activities of caspase-8 and cas pase-3 were determined. Finally, the involvement of oxidative stress in apo ptosis of infected monocytes was investigated. The data indicated that as a consequence of phagocytosis of S. aureus, FasL is released from the monocy te surface and induces apoptosis of phagocytic monocytes and to some extent the bystander cells. The importance of this mechanism was confirmed by dem onstrating that blockage of CD95 prevents S. aureus-induced apoptosis of mo nocytes. Cell death occurring after phagocytosis of S. aureus involves the activation of caspase-3-like proteases, as the specific caspase-3 inhibitor suppressed apoptosis of infected cells. The generation of reactive oxygen intermediates by phagocytic monocytes by itself is not sufficient as a deat h signal but rather acts in up-regulating FasL shedding and possibly in mod ulating caspase activity.