Marine Lectins in Innate Immune Modulation: Mechanistic Insights, Signaling Pathways, and a Cross-Taxa Evidence Landscape

TL;DR

Marine lectins modulate innate immunity through carbohydrate binding and signaling pathways, with bivalve lectins showing strong immune activation and potential for immunotherapy.

Contribution

This review provides a comprehensive synthesis of marine lectin mechanisms, emphasizing bivalve lectins and their signaling pathways in immune modulation.

Findings

Bivalve lectins activate macrophages and pro-inflammatory cytokine production via MAPK, NF-κB, and JAK-STAT pathways.

Marine lectins exhibit context-dependent immune effects, promoting inflammation in resting cells and endotoxin tolerance in activated macrophages.

Functional outcomes include antiviral activity, anti-inflammatory effects, and cancer-related immune responses through glycan recognition.

Abstract

Marine lectins function as pattern recognition receptors in innate immunity through carbohydrate-binding mechanisms. However, mechanistic evidence detailing intracellular signaling cascades (e.g., MAPK/NF-κB/JAK-STAT activation linked to defined cytokine outputs) remains taxonomically uneven. Bivalve mollusks—particularly the Mytilectin family—represent the most extensively characterized group, whereas lectins from other marine phyla (echinoderms, cnidarians, fish, algae) have been studied primarily for structural and glycan-binding properties alongside phenotypic antimicrobial outcomes. Signaling-level resolution in native immune-cell contexts, while present in some cases, remains comparatively limited. This review synthesizes mechanistic insights dominated by bivalve-derived lectins, while integrating cross-taxa comparisons at evidence-supported levels. Specific bivalve lectins induce macrophage activation and pro-inflammatory cytokine production through reactive oxygen species-dependent activation of key signaling pathways including MAPK, NF-κB, and JAK-STAT cascades. These lectins exhibit context-dependent properties, promoting inflammatory responses in resting cells while inducing endotoxin tolerance in pre-activated macrophages through epigenetic reprogramming. Functional outcomes include broad-spectrum antiviral activity through viral envelope glycoprotein binding, anti-inflammatory effects in pain models, and cancer-associated immune responses through tumor glycan recognition and macrophage polarization. Critical gaps include uncharacterized effects on adaptive immunity, limited understanding of dendritic cell and natural killer cell interactions, and incomplete evaluation of cancer immunotherapy potential. Future research should prioritize mechanistic characterization of marine lectin-based immunotherapeutics.

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