Abstract
Humans and other mammals resist exogenous pathogens by recognizing them as non-self. How do they do this? The answer lies in the recognition by mammalian lectin receptors of glycans usually found on the surface of pathogens and whose chemical structure is species-specific. Some glycan components, such as galactofuranose, only occur in microbes, and is the principal means by which mammalian lectin receptors recognize non-self. Several lectins may function together as pattern recognition receptors to survey the infecting pathogen before the adaptive immune system is invoked. Most lectins have primary and secondary monosaccharide-binding sites which together determine the specificity of a receptor toward microbial glycans. There may also be a hydrophobic groove alongside the sugar binding sites that increases specificity. Another elaboration is through oligomerization of lectin domains with defined spacing and arrangement that creates high-affinity binding towards multiply-presented glycans on microbes. Microbe-specific polysaccharides may arise through unique sugar linkages. Specificity can come from mammalian receptors possessing a shallow binding site and binding only internal disaccharide units, as in the recognition of mannan by Dectin-2. The accumulation of 3D structural information on lectins receptors has allowed the recognition modes of microbe glycans to be classified into several groupings. This review is an introduction to our current knowledge on the mechanisms of pathogen recognition by representative mammalian lectin receptors.
Highlights
Glycans are covalently linked to proteins or lipids and are mostly expressed on the cell surface
We here attempt to classify the recognition modes of microbe glycan into four modes: i) recognition of specific group epitope, ii) recognition of oligosaccharide with unique linkage and aglycon, iii) pattern recognition of special arrangements of sugar residues, and iv) internal recognition of polysaccharide (Figure 1). This classification is a starting point for discussion and will be revised according to new findings and inputs. Hereafter these recognition modes are explained by means of 3D structures of representative lectin receptors (Table 1)
How does the mammalian immune system sense microbe glycans as non-self? One possible simple and straightforward strategy is to detect microbe-specific sugar residues not found in mammals
Summary
Institute of Molecular Biomembrane and Glycobiology, Division of Structural Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan Reviewed by: Franck Fieschi, Université Grenoble Alpes, France Frederique Lisacek, Swiss Institute of Bioinformatics (SIB), Switzerland Specialty section: This article was submitted to Structural Biology, a section of the journal Frontiers in Molecular Biosciences
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