Functional characterization of mannose receptor expressed by immunocompetent mouse microglia

Abstract

The mannose receptor is a pattern-recognition receptor involved in innate and adaptive immunity. The receptor is mainly expressed by macrophages and, within the brain, by astrocytes and microglia. This study reports for the first time the effects of two classical proinflammatory (interferon-gamma, IFNgamma) and anti-inflammatory (interleukin-4, IL-4) cytokines on the levels of expression and activity of the mannose receptor expressed by mouse microglia, the brain resident macrophages. As observed for macrophages, IFNgamma treatment led to a decrease and IL-4 to an increase of mannose receptor expression. Consequently, the rates of pinocytosis were strongly upregulated by IL-4 and inhibited by IFNgamma. This latter, however, resumed with time and reached again the constitutive rate of pinocytosis. This recovery resulted from an increased pinocytic activity of the few mannose receptor molecules still expressed by IFNgamma-treated microglia. This may suggest a brain-specific regulation of the effects of IFNgamma since such a phenomenon has not been observed in macrophages. Together, these observations demonstrate that cytokine-stimulated immunocompetent microglia express a functional mannose receptor.

Microglial carbohydrate-binding receptors for neural repair

“…The mannose receptor, mainly expressed by macrophages, astrocytes and microglia (Zimmer et al 2003), is involved in many biological functions such as cell-cell interactions, neutralization of pathogens and endocytosis of glycoproteins. It is a type I transmembrane glycoprotein consisting in an amino-terminal cysteinerich domain, a fibronectin type II repeat, 8 C-type lectin-like domains (CTLDs), a transmembrane domain and a short cytoplasmic tail (Napper et al 2001;Taylor et al 2005).…”

Phagocytic functions of microglial cells in the central nervous system and their importance in two neurodegenerative diseases: multiple sclerosis and Alzheimer’s disease

“…However, rodent cultured microglial cells express MR. Microglial MR expression is upregulated in response to anti-inflammatory substances such as IL-4 or dexamethasone and downregulated after treatment by pro-inflammatory mediators IFNγ or LPS [41,42]. This differential response to anti-or pro-inflammatory molecules has been previously described in peripheral macrophages [38,43,44].…”

“…Indeed, the uptake of heat-killed yeast was reduced in the presence of α-mannans, a commonly used ligand of MR [45,46]. However, primary cultured microglial cells are able to endocyte different mannosylated ligands such as horseradish peroxydase [41,42] and mannosylated-BSA [42] through the MR. Mannosylated molecules are present at the surface of various pathogens and are a pathogen-associated molecular pattern. This suggests that the MR expressed in these primary cultured microglia can bind and eliminate microorganisms by phagocytosis.…”

Mannose Receptor Family: R-Type Lectins

“…Down-regulation of the MR by IFN-g is concomitant with the induction of the invariant chain, which is also induced by GM-CSF + IL-4. MR-expressing astrocytes may act as scavenger not only in CNS development but also in defense, against soluble and particulate mannosylated pathogens, presenting fragments there of at strategic locations in the CNS (Burudi et al 1999;Zimmer et al 2003).…”