THE (ALPHA-2-]8)-LINKED POLYSIALIC ACID CAPSULE OF GROUP-B NEISSERIA-MENINGITIDIS MODIFIES MULTIPLE STEPS DURING INTERACTION WITH HUMAN MACROPHAGES

Group B Neisseria meningitidis causes systemic disease, including meni ngitis, after initial colonization and subsequent penetration of nasop haryngeal mucose, a tissue which is richly populated by macrophages. I n an initial effort to characterize the interaction of N. meningitidis and mature human macrophages, the influence of the (alpha 2-->8)-link ed polysialic acid capsule on the interaction of N. meningitidis with human monocyte-derived macrophages was investigated with a capsulate c ase isolate and an isogenic Tn916-derived noncapsulate transformant. T he capsulate strain was fourfold less adherent to the macrophage surfa ce after cold incubation, although adherence of both strains was signi ficantly increased after opsonization with nonimmune C5-depleted serum . When opsonized inocula mere adjusted so that they adhered to matroph ages in equal numbers, the two strains were internalized at equivalent rates and both entered membrane-bound compartments (phagosomes). Colo calization of bacteria with the late endosomal and lysosomal marker ly sosome-associated membrane protein revealed that fusion of lyososomes with phagosomes containing the capsulate organism was significantly re duced 10 and 30 min after entry, but by 1 h, no difference between the strains was observed. Once internalized, meningococci were effectivel y killed, although more rapid killing of the capsulate strain was obse rved over the first 3 h. These results indicate that the (alpha 2->8)- linked polysialic arid capsule modifies the interaction of meningococc i with human macrophages at multiple steps, including adherence to the macrophage surface and phagosome-lysosome fusion. Moreover, the disco rdance 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. meningitids.