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Mannose-binding lectin enhances phagocytosis and killing of Neisseria meningitidis by human macrophages

Mannose-binding lectin enhances phagocytosis and killing of Neisseria meningitidis by human macrophages
Mannose-binding lectin enhances phagocytosis and killing of Neisseria meningitidis by human macrophages

Deficiency of mannose-binding lectin (MBL) is probably the most common human immunodeficiency and is associated with an increased risk of mucosally acquired infections including meningococcal disease. Tissue macrophages are an important component of mucosal defense, and so we determined the effect of MBL on uptake of meningococci by human monocyte-derived macrophages. Opsonization with MBL significantly increased the capture and doubled the amount of internalization of Neisseria meningitidis. Inhibition of f-actin polymerization indicated that MBL exerted this effect by a dose-dependent acceleration of uptake into phagosomes, which was maximal within the normal physiological concentration of MBL (1.5 microg/ml) and was independent of scavenger receptors. MBL accelerated the acquisition and subsequent loss of the early endosome marker, early endosomal antigen-1, and enhanced the acquisition of the late endosomal marker, lysosome-associated membrane protein-1. MBL reduced the survival of meningococci within macrophages by more than half, despite the increased uptake of organisms, and significantly reduced the number of viable extracellular bacteria by 80%. We conclude that MBL is a dependent opsonin able to accelerate microbial uptake and killing. These results suggest that MBL could modify disease susceptibility by modulating macrophage interactions with mucosal organisms at the site of initial acquisition.

Cells, Cultured, Cytotoxicity Tests, Immunologic, Humans, Macrophages, Mannose-Binding Lectin, Neisseria meningitidis, Opsonin Proteins, Phagocytosis, Journal Article, Research Support, Non-U.S. Gov't
0741-5400
328-36
Jack, Dominic L
246dc47b-5b5e-4933-9227-d13aafd9cb88
Lee, Margaret E
a87d108c-c8e3-420c-be05-e7e23ee0619e
Turner, Malcolm W
b6698cdf-bdd0-44f9-a152-0e3657833fff
Klein, Nigel J
f01b50e5-cb25-4558-99aa-b697d534fb55
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Jack, Dominic L
246dc47b-5b5e-4933-9227-d13aafd9cb88
Lee, Margaret E
a87d108c-c8e3-420c-be05-e7e23ee0619e
Turner, Malcolm W
b6698cdf-bdd0-44f9-a152-0e3657833fff
Klein, Nigel J
f01b50e5-cb25-4558-99aa-b697d534fb55
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Jack, Dominic L, Lee, Margaret E, Turner, Malcolm W, Klein, Nigel J and Read, Robert C (2005) Mannose-binding lectin enhances phagocytosis and killing of Neisseria meningitidis by human macrophages. Journal of Leukocyte Biology, 77 (3), 328-36. (doi:10.1189/jlb.0604342).

Record type: Article

Abstract

Deficiency of mannose-binding lectin (MBL) is probably the most common human immunodeficiency and is associated with an increased risk of mucosally acquired infections including meningococcal disease. Tissue macrophages are an important component of mucosal defense, and so we determined the effect of MBL on uptake of meningococci by human monocyte-derived macrophages. Opsonization with MBL significantly increased the capture and doubled the amount of internalization of Neisseria meningitidis. Inhibition of f-actin polymerization indicated that MBL exerted this effect by a dose-dependent acceleration of uptake into phagosomes, which was maximal within the normal physiological concentration of MBL (1.5 microg/ml) and was independent of scavenger receptors. MBL accelerated the acquisition and subsequent loss of the early endosome marker, early endosomal antigen-1, and enhanced the acquisition of the late endosomal marker, lysosome-associated membrane protein-1. MBL reduced the survival of meningococci within macrophages by more than half, despite the increased uptake of organisms, and significantly reduced the number of viable extracellular bacteria by 80%. We conclude that MBL is a dependent opsonin able to accelerate microbial uptake and killing. These results suggest that MBL could modify disease susceptibility by modulating macrophage interactions with mucosal organisms at the site of initial acquisition.

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More information

e-pub ahead of print date: 29 November 2004
Published date: March 2005
Keywords: Cells, Cultured, Cytotoxicity Tests, Immunologic, Humans, Macrophages, Mannose-Binding Lectin, Neisseria meningitidis, Opsonin Proteins, Phagocytosis, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416426
URI: http://eprints.soton.ac.uk/id/eprint/416426
ISSN: 0741-5400
PURE UUID: 7d9ba57f-cf5a-42fb-b4ee-cdd559af3c01
ORCID for Robert C Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 15 Dec 2017 17:30
Last modified: 10 Nov 2021 03:30

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Contributors

Author: Dominic L Jack
Author: Margaret E Lee
Author: Malcolm W Turner
Author: Nigel J Klein
Author: Robert C Read ORCID iD

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