title: Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis.
abstract: Apoptosis of macrophages may be a pathogen-directed mechanism of immune escape or may represent appropriate host response to infection. Human monocyte-derived macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-level constitutive apoptosis, but culture of MDMs with opsonized serotype I Streptococcus pneumoniae (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis was associated with phagocytosis of bacteria and intracellular killing that was blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody. Paraformaldehyde-fixed I-MDMs induced apoptosis in uninfected syngeneic monocytes at levels greater than those in monocytes incubated alone or incubated with fixed C-MDMs. Apoptosis of syngeneic monocytes was blocked by anti-Fas antibody. The immune response of macrophages to S. pneumoniae includes a novel form of apoptosis that is associated with successful phagocytosis and bacterial killing. This response in vivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae.
authors.affiliation: Division of Genomic Medicine, University of Sheffield Medical School, Sheffield S10 2RX, United Kingdom. d.h.dockrell@shef.ac.uk
authors.forename: D H
authors.initials: DH
authors.lastname: Dockrell
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: D H
authors.initials: DH
authors.lastname: Lynch
authors.forename: R C
authors.initials: RC
authors.lastname: Read
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D012016:Reference Values; D012044:Regression Analysis; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013997:Time Factors
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone