Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis

Apoptosis of macrophages may be a pathogen-directed mechanism of immune esc ape or may represent appropriate host response to infection. Human monocyte -derived macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-leve l constitutive apoptosis, but culture of MDMs with opsonized serotype I Str eptococcus pneumoniae (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis was associated with phagocytosis of bacteria an d intracellular killing that was blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody. Paraformaldehyde-fixed I-MDMs induced ap optosis in uninfected syngeneic monocytes at levels greater than those in m onocytes incubated alone or incubated with fixed C-MDMs. Apoptosis of synge neic monocytes was blocked by anti-Fas antibody. The immune response of mac rophages to S. pneumoniae includes a novel form of apoptosis that is associ ated with successful phagocytosis and bacterial killing. This response in v ivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae.