title: Streptococcus pneumoniae-associated human macrophage apoptosis after bacterial internalization via complement and Fcgamma receptors correlates with intracellular bacterial load.
abstract: Opsonization enhances Streptococcus pneumoniae-induced human monocyte-derived macrophage (MDM) apoptosis. Both depletion of complement and immunoglobulin from opsonizing serum and blockade of the macrophages CR1, CR3, FcgammaRII, and FcgammaRIII partially decreased MDM apoptosis after S. pneumoniae phagocytosis, and these effects correlated with reduced numbers of internalized bacteria. Chloramphenicol inhibition of protein synthesis by opsonized S. pneumoniae down-regulated subsequent MDM apoptosis. Phagocytosis of an unencapsulated mutant of S. pneumoniae resulted in increased MDM apoptosis, in association with enhanced internalization. Caspase inhibition was associated with decreased killing of bacteria. Enhanced induction of apoptosis by opsonized S. pneumoniae is the result of increased intracellular burden of bacteria, rather than of a specific pattern of engagement of complement receptor or FcgammaR. A dynamic interaction between live intracellular bacteria and the host cell is necessary for induction of apoptosis in MDMs, and induction of apoptosis contributes to the host defense against S. pneumoniae.
authors.affiliation: Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, United Kingdom.
authors.forename: Farzana
authors.initials: F
authors.lastname: Ali
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Lee
authors.forename: Francesco
authors.initials: F
authors.lastname: Iannelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
authors.forename: David H
authors.initials: DH
authors.lastname: Dockrell
mesh_terms: D017209:Apoptosis; D005434:Flow Cytometry; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000382:microbiology*; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000382:microbiology; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis; D011018:Pneumonia, Pneumococcal / Q000382:microbiology; D011951:Receptors, Complement / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D009895:Opsonin Proteins; D011951:Receptors, Complement; D017452:Receptors, IgG