Mannose-binding lectin enhances phagocytosis and killing ofNeisseria meningitidisby human macrophages

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.

Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A

“…MBL-deficient mice have been shown to be susceptible to infection of S. aureus, demonstrating the key role of MBL in S. aureus infection (30). One recent study indicates that MBL also acts as an opsonin (31). Opsonization with MBL significantly increases the internalization of Neisseria meningitidis and reduces the survival of meningococci within macrophages.…”

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

“…However, the thick collagenous cuticle of Mf is unlikely to be susceptible to the pore-forming qualities of the membrane-attack complex of complement. In addition, although MBL-A is known to augment opsonization and phagocytosis of certain microbes (17), Mf are too large (170 -230 m in length) to be phagocytosed and therefore enhanced survival of Mf in the absence of MBL-A is unlikely to result from reduced phagocytosis. We therefore examined several immunological parameters in the MBL-A Ϫ/Ϫ mice to determine whether absence of MBL-A interfered with the induction of other immune responses.…”

Mannose-binding lectin is present in human semen and modulates cellular adhesion of Neisseria gonorrhoeae in vitro

“…MBL activates complement via MBL-associated serum proteases (MASPs), which cleave C2 and C4 to form a C3 convertase leading to higher levels of serum killing and opsonization [5,6]. However, MBL also has a number of complementindependent effects on bacterial adhesion, internalization [7][8][9] and the inflammatory response elicited by a number of pathogens [10,11]. MBL is an acute phase protein produced mainly by the liver, but gene transcription has been demonstrated recently to occur in extra-hepatic sites, including the testis and the prostate gland [12].…”