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

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.

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

“…Preliminary data support the putative interaction of rmS5D-SRCRB-HA with some extracellular matrix proteins, such as laminin and, to a lesser extent, fibronectin, but not collagen I or IV. Moreover, we also provide evidence on the carbohydrate-dependent interaction of mS5D-SRCRB-HA with galectin-1, a host soluble lectin that functions as a damage-associated molecular pattern and a receptor for PAMPs (35). The mucosal-defense properties of mouse S5D-SRCRB against living organisms are supported by its broad binding and aggregating microbial spectrum that includes saprophytic and pathogenic bacteria and fungi; potential interactions with viruses remain to be studied.…”

Galectin-3 Is Required for Resident Microglia Activation and Proliferation in Response to Ischemic Injury

“…Galectin-3 is composed of the C-terminal CRD and the N-terminal nonlectin domain, which is involved in the oligomerization of galectin-3 upon binding to its glycan ligands on cell surfaces (Rabinovich and Toscano, 2009;Sato et al, 2009). During innate and adaptive immune response, galectin-3 can be expressed by variety of immune cells at the periphery (Leffler et al, 2004;Rabinovich et al, 2007;Marth and Grewal, 2008;Yang et al, 2008;Rabinovich and Toscano, 2009).…”

Dangers Within

“…Other candidate DAMPs include galectins 58,59 ; ATP and adenosine 60 -64 ; thioredoxin, a ubiquitous antioxidant enzyme 65,66 ; the intranuclear cytokine, IL-33 67 ; and Tamm-Horsfall protein (THP; or uromodulin), a glycoprotein expressed in the thick ascending limb that is excreted into the urine after proteolytic cleavage. THP is the most abundant protein in urine, but its function remains unclear 68 ; it has been implicated as a biomarker of kidney disease and allograft rejection 69,70 and may be a damage signal in renal tubular injury.…”