title: The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis modifies multiple steps during interaction with human macrophages.
abstract: Group B Neisseria meningitidis causes systemic disease, including meningitis, after initial colonization and subsequent penetration of nasopharyngeal mucosa, a tissue which is richly populated by macrophages. In an initial effort to characterize the interaction of N. meningitidis and mature human macrophages, the influence of the alpha2-->8) -linked polysialic acid capsule on the interaction of N. meningitidis with human monocyte-derived macrophages was investigated with a capsulate case isolate and an isogenic Tn916-derived noncapsulate transformant. The capsulate strain was fourfold less adherent to the macrophage surface after cold incubation, although adherence of both strains was significantly increased after opsonization with nonimmune C5-depleted serum. When opsonized inocula were adjusted so that they adhered to macrophages in equal numbers, the two strains were internalized at equivalent rates and both entered membrane-bound compartments (phagosomes). Colocalization of bacteria with the late endosomal and lysosomal marker lysosome-associated membrane protein revealed that fusion of lysosomes with phagosomes containing the capsulate organism was significantly reduced 10 and 30 min after entry, but by 1 h, no difference between the strains was observed. Once internalized, meningococci were effectively killed, although more rapid killing of the capsulate strain was observed over the first 3 h. These results indicate that the (alpha2-->8)-linked polysialic acid capsule modifies the interaction of meningococci with human macrophages at multiple steps, including adherence to the macrophage surface and phagosome-lysosome fusion. Moreover, the discordance between the kinetics of phagosome- lysosome fusion and bacterial killing suggests that a nonlysosomal mechanism may be responsible for a significant fraction of macrophage killing of N. meningitidis.
authors: Division of Infectious Diseases, University of California, San Francisco, San Francisco General Hospital, 94110, USA.
authors: R C
authors: RC
authors: Read
authors: S
authors: S
authors: Zimmerli
authors: C
authors: C
authors: Broaddus
authors: D A
authors: DA
authors: Sanan
authors: D S
authors: DS
authors: Stephens
authors: J D
authors: JD
authors: Ernst
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes; D008264:Macrophages / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016254:Mutagenesis, Insertional; D009345:Neisseria meningitidis / Q000145:classification / Q000502:physiology*; D010587:Phagocytosis; D010588:Phagosomes; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D012794:Sialic Acids; C021319:polysialic acid