Thus, the disappearance of MGL1 was likely to be attributable to its down-regulation, although the possibility that MGL1-positive macrophages migrated to other regions could not be eliminated. Similarly, expression of MGL on bone marrow-derived Pazopanib structure DCs was previously shown to be abrogated after maturation by lipopolysaccharide,19 and absence of MGL1 expression in the late phase of colitis might be a consequence of activation with several stimuli. The immunological significance of this down-modulation of MGL1 remains unclear. To date, many reports have shown that C-type lectins interact with microorganisms and are involved in endocytosis, signal transduction, and opsonization.12 Pathogenic microorganisms have been shown to use these lectins for their infection,32 as observed with human MGL acting as an entry site for filovirus.

33 MGL1 should be considered unique among the C-type lectins expressed on macrophages and DCs because of its distinct carbohydrate specificity. Mannose or glucose residues on the surface of pathogens have been found to be reactive with lectins, such as macrophage mannose receptor, DC-SIGN, and dectin-1, whereas MGL1 binds specifically to terminal Gal and GalNAc residues as a monosaccharide. Previously, a soluble lectin expressed in the intestine, intelectin, was shown to bind to Nocardia rubra and the binding was inhibited by the addition of Gal,34 although the biological consequence of the binding of bacteria to this lectin is unknown. The present report is the first to demonstrate the role of a Gal-type C-type lectin in the recognition of commensal bacteria.

The presence of the Gal/GalNAc residue in the cell wall polysaccharide of streptococci has been reported.35 Co-aggregation of Streptococcus viridans, a member of the oral flora, was inhibited by the addition of oligosaccharides containing Gal and/or GalNAc,36 strongly suggesting that Gal/GalNAc residues were exposed on the surfaces of Streptococci. Another study showed that Gal and GalNAc residues were present in an exo-polysaccharide or a capsular polysaccharide produced by Lactobacillus.37 Bacteria have been known to produce many types of glycoproteins. The carbohydrate structures are different depending on the species and environments,38 although it is still unclear which glycoprotein is reactive to MGL1.

Possible mechanisms of regulation of cytokine expression by MGL1 may be mediated by the YXXL motif in the cytoplasmic tail. MGL1, MGL2, Dectin-1, and DC-SIGN have been previously shown to contain similar motifs in the cytoplasmic domain, and IL-10 expression has been reported to be induced by the signals from the YXXL motif of Dectin-1.39,40 However, possible signal transduction through MGL1/2 was not previously reported. Alternatively, MGL1 might be involved with the modulation of signals Brefeldin_A through pathogen recognition receptors. Constitutive signals from commensal bacteria through TLRs and MyD88 were reported to be necessary to suppress colitis.