Galectins in innate immunity: dual functions of host soluble β‐galactoside‐binding lectins as damage‐associated molecular patterns (DAMPs) and as receptors for pathogen‐associated molecular patterns (PAMPs)

Abstract

Summary: The glycocalyx is a glycan layer found on the surfaces of host cells as well as microorganisms and enveloped virus. Its thickness may easily exceed 50 nm. The glycocalyx does not only serve as a physical protective barrier but also contains various structurally different glycans, which provide cell‐ or microorganism‐specific ‘glycoinformation’. This information is decoded by host glycan‐binding proteins, lectins. The roles of lectins in innate immunity are well established, as exemplified by collectins, dectin‐1, and dendritic cell (DC)‐specific intracellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN). These mammalian lectins are synthesized in the secretory pathway and presented on the cell surface to bind to specific glycan ‘epitopes’. As they recognize non‐self glycans presented by microorganisms, they can be considered as receptors for pathogen‐associated molecular patterns (PAMPs), i.e. pattern recognition receptors (PRRs). One notable exception is the galectin family. Galectins are synthesized and stored in the cytoplasm, but upon infection‐initiated tissue damage and/or following prolonged infection, cytosolic galectins are either passively released by dying cells or actively secreted by inflammatory activated cells through a non‐classical pathway, the ‘leaderless’ secretory pathway. Once exported, galectins act as PRR, as well as immunomodulators (or cytokine‐like modulators) in the innate response to some infectious diseases. As galectins are dominantly found in the lesions where pathogen‐initiated tissue damage signals appear, this lectin family is also considered as potential damage‐associated molecular pattern (DAMP) candidates that orchestrate innate immune responses alongside the PAMP system.