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.
Jack
Dominic L
DL
University of Sheffield Medical School, Beech Hill Road, Sheffield, UK, S10 2RX. D.L.Jack@sheffield.ac.uk
Lee
Margaret E
ME
Turner
Malcolm W
MW
Klein
Nigel J
NJ
Read
Robert C
RC
D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D037601:Mannose-Binding Lectin / Q000494:pharmacology*; D009345:Neisseria meningitidis / Q000254:growth & development / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology*
D037601:Mannose-Binding Lectin; D009895:Opsonin Proteins