Identification of multiple galectins as receptors for β-1,3-glucans

β-1,3-glucans are natural polysaccharides widely distributed in bacterial capsules and fungal cell walls. β-1,3-glucans are potent immunomodulators traditionally recognized by receptors like Dectin-1 and CD204, yet the complete receptor repertoire has remained ill-defined. Here, we identify several galectins (Gal-1, -2, -3, -4, -7, -8, -9) as receptors for β-1,3-glucans. Using hemagglutination inhibition, biolayer interferometry (BLI), and microscale thermophoresis (MST) assays, we demonstrate the binding of galectins to β-1,3-glucans from yeast, bacteria, Lentinus edodes , and Ganoderma lucidum . The affinity (K_D) of these interactions ranges from nanomolar to micromolar. Notably, the affinities of β-1,3-glucans for galectins are comparable to or exceed the affinities for Dectin-1 and CD204. Additionally, β-1,3-glucan modulates galectin-mediated cell activation and apoptosis. Our findings not only expand the receptor repertoire of β-1,3-glucans and deepen our understanding of their immunomodulatory mechanisms, but they also indicate that galectins are promising therapeutic targets for regulating β-1,3-glucan-mediated immune responses, such as in anti-fungal therapy and cancer immunotherapy.