The mannose-binding lectin: a prototypic pattern recognition molecule

Abstract

The innate immune system is comprised of a sophisticated network of recognition and effector molecules that act together to protect the host in the first minutes or hours of exposure to an infectious challenge. The mannose-binding lectin (MBL) is an evolutionary conserved circulating host defense protein that acts as a broad-spectrum recognition molecule against a wide variety of infectious agents. Target binding triggers the MBL pathway of complement activation. MBL can be considered conceptually as an 'ante-antibody' because it has a role in mammals during the lag period that is required to develop an antibody response against infectious agents. Additionally, there are MBL-like homologues in animals that lack adaptive immunity that activate a primitive complement system, and under these circumstances these MBL-like molecules play an analogous role to antibodies in higher animals. These molecules might be considered to be functional antecedents of antibodies. Recent work also indicates that MBL recognizes altered self-antigens, and as such MBL has a role that extends beyond a traditional role in first line host defense as it appears to play a role as a modulator of inflammation.

Agalactosylated IgG antibodies depend on cellular Fc receptors forin vivoactivity

“…More importantly, antibody activity of both IgG-G0 isotypes was fully intact in MBL-null mice, which completely lack MBL activity, suggesting that, despite the capacity to bind MBL and activate the complement cascade in vitro, there was no significant contribution of MBL to the activity of IgG-G0 antibodies in vivo. The MBL or lectin pathway of complement activation converges with the classical and alternative pathways with the activation of complement component C3 (22,34). We therefore further analyzed the contribution of the complement component C3 to determine whether any complement activation pathway contributed to the in vivo activity of IgG antibodies lacking galactose by using C3-deficient mice.…”

“…MBL is the first component of the lectin pathway of complement activation and can bind to terminal fucose, glucose, mannose, or N-acetylglucosamine, but not to galactose residues. MBL also directly recognizes a variety of pathogenic microorganisms including Gram-positive and -negative bacteria, yeast, mycobacteria, parasites, and viruses (21,22). In addition, mice and humans with functionally impaired or deleted MBL are more susceptible to infections (23,24).…”

Identification of the Site of Human Mannan-Binding Lectin Involved in the Interaction with Its Partner Serine Proteases: The Essential Role of Lys55

“…M annan-binding lectin (MBL), 3 a member of the collectin family, is an oligomeric C-type lectin that recognizes and binds patterns of neutral carbohydrates such as mannose and N-acetylglucosamine present on the surface of pathogens (1,2). It is a major actor of innate immunity, due to its ability to opsonize pathogens and thereby enhance their phagocytosis, and to activate the complement cascade via the lectin pathway (3).…”

Conformational Changes in Mannan-Binding Lectin Bound to Ligand Surfaces

“…Binding by MBL to microbial surfaces activates the complement system, which leads to the deposition of a cascade of plasma proteins that facilitates uptake by leukocytes or lysis of the microbe. Recent studies also suggest a role for MBL in the clearance of apoptotic cells and the elimination of tumor cells (2,3).…”