Abstract

Lectins are important components of an effective innate immune system. The C-type and pentraxin families of lectins act as pattern recognition receptors, fix complement, serve as opsonins, and have direct microbicidal activity. Less is known about the antimicrobial functions of the galectins and the X-lectins. Several roles for galectins in regulating neutrophil, dendritic cell, and lymphocyte function are known. Some galectins are also known to recognize pathogen-associated saccharide ligands. The prototypic X-lectin participates in the block to polyspermy during fertilization. Although galectin and X-lectin expression correlate with microbial infection, no direct antimicrobial activity has been reported for either family of lectins.

I have identified novel antimicrobial functions for members of the galectin and the X-lectin families of lectins. Galectin-1 inhibited Nipah virus envelope glycoprotein-mediated cell fusion. Galectin-1 bound to Nipah virus envelope glycoproteins F (NiV-F) and G (NIV-G), resulting in increased oligomerization of the F and G glycoproteins. This was the fist report of inhibition of viral glycoprotein-mediated cell fusion for a galectin family member. Furthermore, I have found new anti-fungal functions for galectin-3 and HL-2. I found that galectin-3, but not galectin-1, bound to Candida strains that expressed different types of β-1,2-linked oligomannan structures, and galectin-3 did not bind to Saccharomyces cerevisiae that lacks β-1,2-linked oligomannans. Moreover, galectin-3 binding resulted in death of Candida strains that expressed a specific subset of the β-1,2-linked oligomannan structures. I also found that HL-2, an X-lectin family member expressed in Paneth cells of the small intestine, bound fungal pathogens but not bacterial pathogens. Similarly to galectin-3, binding of HL-2 killed Candida albicans. In summary, my findings demonstrate novel functions for members of the galectin and the X-lectin families of lectins that indicate that these lectins participate in microbial recognition and clearance, contributing to the host innate immune defense against pathogens.