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The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis modifies multiple steps during interaction with human macrophages

The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis modifies multiple steps during interaction with human macrophages
The (alpha2-->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 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.

Antigens, CD, Bacterial Adhesion, Bacterial Capsules, Humans, Lysosome-Associated Membrane Glycoproteins, Lysosomes, Macrophages, Membrane Glycoproteins, Microscopy, Confocal, Microscopy, Fluorescence, Mutagenesis, Insertional, Neisseria meningitidis, Phagocytosis, Phagosomes, Sialic Acids, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.
0019-9567
3210-3217
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Zimmerli, S.
0f75a5e3-ee23-44cf-a9d5-e606b455338a
Broaddus, C.
2c83f4e8-b103-4866-8652-708ccaa75a23
Sanan, D.A.
e2e80596-55f9-4221-be4d-c0c35fbf8d73
Stephens, D.S.
52a6c778-22d8-4cf5-ac26-7cbdf0a2e7f2
Ernst, J.D.
89065f3c-d2fd-47fb-818d-30b440f69e89
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Zimmerli, S.
0f75a5e3-ee23-44cf-a9d5-e606b455338a
Broaddus, C.
2c83f4e8-b103-4866-8652-708ccaa75a23
Sanan, D.A.
e2e80596-55f9-4221-be4d-c0c35fbf8d73
Stephens, D.S.
52a6c778-22d8-4cf5-ac26-7cbdf0a2e7f2
Ernst, J.D.
89065f3c-d2fd-47fb-818d-30b440f69e89

Read, R.C., Zimmerli, S., Broaddus, C., Sanan, D.A., Stephens, D.S. and Ernst, J.D. (1996) The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis modifies multiple steps during interaction with human macrophages. Infection and Immunity, 64 (8), 3210-3217.

Record type: Article

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.

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More information

Published date: August 1996
Keywords: Antigens, CD, Bacterial Adhesion, Bacterial Capsules, Humans, Lysosome-Associated Membrane Glycoproteins, Lysosomes, Macrophages, Membrane Glycoproteins, Microscopy, Confocal, Microscopy, Fluorescence, Mutagenesis, Insertional, Neisseria meningitidis, Phagocytosis, Phagosomes, Sialic Acids, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.

Identifiers

Local EPrints ID: 417319
URI: https://eprints.soton.ac.uk/id/eprint/417319
ISSN: 0019-9567
PURE UUID: 0b039b32-25bf-4366-94a7-b9648309da46
ORCID for R.C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 29 Jan 2018 17:30
Last modified: 14 Mar 2019 01:36

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