Mannose-Binding Lectin and Innate Immune Mechanisms

Mannose-binding lectin (MBL) is a soluble C-type lectin that recognises carbohydrate patterns on a wide range of pathogens and initiates the lectin pathway of complement activation. Upon binding to mannose and related sugars on microbial surfaces, MBL forms complexes with MBL-associated serine proteases (MASPs), triggering a proteolytic cascade that generates C3 convertase, promotes opsonisation and drives formation of the membrane attack complex. Beyond direct pathogen clearance, MBL and its associated lectin pathway interact with coagulation factors, influence inflammation and contribute to tissue homeostasis and repair. Genetic polymorphisms in MBL can modulate circulating levels and functional activity, with implications for susceptibility to infections, inflammatory disorders and ischaemia-reperfusion injury. Recent work has also highlighted non-canonical roles of lectin-pathway components in embryonic development, tumour biology and regulation of the alternative complement pathway. Together, these findings underline the central place of MBL in innate immunity, bridging early host defence, inflammatory regulation and cross-talk with other proteolytic systems.

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Mannose-Binding Lectin and Innate Immune Mechanisms publication trend

The graph below shows the total number of articles in mannose-binding lectin and innate immune mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Mannose-binding lectin (MBL): A soluble C-type lectin that recognises pathogen surface carbohydrates and initiates the lectin complement pathway.

Complement system: A proteolytic cascade of plasma proteins that enhances pathogen clearance, inflammation and cell lysis through three activation pathways.

Lectin pathway: One of three complement activation routes, triggered by carbohydrate recognition molecules such as MBL and ficolins complexed with MASPs.

MBL-associated serine proteases (MASPs): Proteolytic enzymes (MASP-1, MASP-2, MASP-3) that, upon MBL binding, cleave complement components C4 and C2 to form C3 convertase.

Pattern-recognition molecules (PRMs): Innate immune receptors, including MBL, collectins and ficolins, that detect conserved molecular patterns on pathogens.

Opsonisation: Tagging of pathogens by complement fragments (e.g., C3b) or antibodies to facilitate phagocytosis by immune cells.

References

1. Ficolin-A induces macrophage polarization to a novel pro-inflammatory phenotype distinct from classical M1. Cell Communication and Signaling (2024).
2. Collectin-11 promotes cancer cell proliferation and tumor growth. JCI Insight (2023).
3. Development and characterization of narsoplimab, a selective MASP-2 inhibitor, for the treatment of lectin-pathway–mediated disorders. Frontiers in Immunology (2023).
4. The Lectin Pathway of the Complement System—Activation, Regulation, Disease Connections and Interplay with Other (Proteolytic) Systems. International Journal of Molecular Sciences (2024).
5. Simultaneous Activation of Complement and Coagulation by MBL-Associated Serine Protease 2. PLOS ONE (2007).
6. Effects of MASP-1 of the Complement System on Activation of Coagulation Factors and Plasma Clot Formation. PLOS ONE (2012).
7. COLEC10 is mutated in 3MC patients and regulates early craniofacial development. PLOS Genetics (2017).
8. MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked. Scientific Reports (2016).