Microglial carbohydrate-binding receptors for neural repair

Microglia are the resident immune cells of the central nervous system (CNS) and perform typical scavenging and innate immune functions. Their capacity to eliminate extracellular aggregates and apoptotic neural material without inflammation is crucial for brain tissue homeostasis and repair. To fulfill these tasks, microglia express a whole set of recognition receptors including toll-like (TLRs), carbohydrate-binding, Fc, complement and cytokine receptors. Receptors recognizing carbohydrate structures are strongly involved in microglial repair function. Carbohydrate-binding receptors can be divided into two major subgroups: the sulfated glycosaminoglycan (SGAG)-binding receptors and the lectins (Siglecs, galectins, selectins). SGAG-binding receptors recognize anionic structural motifs within extended SGAG chains. Siglecs bind to the sialic acid cap of the intact glycocalyx. Other lectin family members such as galectins recognize lactosamine units typically exposed after alteration of the glycocalyx. Dependent on the type of microglial carbohydrate-binding receptors that are stimulated, either a pro-inflammatory cytotoxic or an anti-inflammatory repair-promoting response is evoked. The carbohydrate-binding receptors are also crucial in regulating microglial function such as phagocytosis during neurodegenerative or neuroinflammatory processes. A balance between microglial carbohydrate-binding receptor signaling via an immunoreceptor tyrosine-based activation motif or an immunoreceptor tyrosine-based inhibitory motif is required to polarize microglial cells appropriately so that they create a microenvironment permissive for neural regenerative events.