Microglial carbohydrate-binding receptors for neural repair

Abstract

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.

Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects

“…Array implantation also causes an early activation and migration of microglial cells towards the microelectrodes, which could reflect highly specific interactions mediated by selectins, integrins, cytokines and carbohydrate-binding receptors (Kaur et al, 2010; Linnartz et al, 2012). These microglial cells are very sensitive to pathological conditions, even if they respond only to variations in local extracellular ionic concentrations (Kreutzberg, 1996; Freire et al, 2011) and we have found that there is a rapid activation, in a matter of minutes, of these cells in human brain.…”

Glycosaminoglycans in infectious disease

“…The carbohydrate-binding receptors can be divided into two major subgroups, GAG-binding receptors and lectins (Mulloy & Linhardt, 2001;Esko & Selleck, 2002;Drickamer & Taylor, 2003;Varki & Angata, 2006). The lectins can be further subdivided into three major classes: galectins, siglecs and selectins (Schnaar, 2004;Linnartz, Bodea & Neumann, 2012). There is extensive evidence that GAGs promote microbial pathogenesis and invasion (Rostand & Esko, 1997) by interacting with bacteria (e.g.…”

Molecular basis of neural repair mechanisms

“…Moreover, carbohydratebinding receptors of the sulphated-glycosaminoglycanbinding group or the lectin subgroup including siglecs, galectins and selectins seem to play a crucial role in microglial reactivity and repair functions. Linnartz et al (2012) unravel the decisive role of these microglial receptors in the stimulation of either pro-inflammatory cytotoxic or anti-inflammatory repair-promoting responses. As has become obvious in recent years, the infiltration and activation of numerous cell types in CNS trauma and stroke are orchestrated by chemokines and their receptors.…”