Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE98826 | GEO | 2017/08/25
SECONDARY ACCESSION(S): PRJNA386319
REPOSITORIES: GEO
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Project description:C-type lectin receptors (CLRs) comprise a large family of immunoreceptors that recognize polysaccharide ligands exposed on pathogen surfaces and are conserved among mammals. However, interspecies differences in their ligand spectrums are not fully understood. Dectin-1 is a well-characterized CLR that recognizes ?-glucan. We report here that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. Low-valency ?-glucan components within fucan appeared to be responsible for this activation, as the ligand activity was eliminated by ?-glucanase treatment. The low-valency ?-glucan laminarin also acted as an agonist for human Dectin-1 but not for mouse Dectin-1, whereas the high-valency ?-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 does not determine its unique sensitivity to low-valency ?-glucan. Rather, we found that its intracellular domain renders human Dectin-1 reactive to low-valency ?-glucan ligand. Substitution with two amino acids, Glu2 and Pro5, located in the human Dectin-1 intracellular domain was sufficient to confer sensitivity to low-valency ?-glucan in mouse Dectin-1. Conversely, the introduction of mouse-specific amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity to low-valency ?-glucan. Indeed, low-valency ligands induced a set of proinflammatory genes in human but not mouse dendritic cells. These results suggest that the intracellular domain, not ligand-binding domain, of Dectin-1 determines the species-specific ligand profile.
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Project description:C-type lectin receptors (CLRs) are a large family of immunoreceptors that recognizes polysaccharides exposed on pathogens and triggers innate immune responses. However, the ligand spectrums of the whole members have not been fully understood. In this study, we found that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. In fucan, low-valency β-glucan appeared to represent this activity, as the ligand activity was eliminated by the treatment of westase, a β-glucanase. Another low-valency β-glucan, laminarin, also acts as an agonist on human Dectin-1 but not for mouse Dectin-1, whereas high-valency β-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 did not determine its unique sensitivity to low-valency β-glucan. Rather, its intracellular domain contributes to render human Dectin-1 reactive to low-valency β-glucan. Within the hDectin-1 intracellular domain, only two amino acids, Glu2 and Pro5, were sufficient to confer sensitivity on mouse Dectin-1. Conversely, the introduction of mouse-type amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity. These results suggest that the intracellular domain, but not the ligand binding domain, of Dectin-1 modulate their functions which determine the ligand spectrum.
2017-08-25 | GSE98825 | GEO
Project description:C-type lectin receptors (CLRs) are a large family of immunoreceptors that recognizes polysaccharides exposed on pathogens and triggers innate immune responses. However, the ligand spectrums of the whole members have not been fully understood. In this study, we found that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. In fucan, low-valency β-glucan appeared to represent this activity, as the ligand activity was eliminated by the treatment of westase, a β-glucanase. Another low-valency β-glucan, laminarin, also acts as an agonist on human Dectin-1 but not for mouse Dectin-1, whereas high-valency β-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 did not determine its unique sensitivity to low-valency β-glucan. Rather, its intracellular domain contributes to render human Dectin-1 reactive to low-valency β-glucan. Within the hDectin-1 intracellular domain, only two amino acids, Glu2 and Pro5, were sufficient to confer sensitivity on mouse Dectin-1. Conversely, the introduction of mouse-type amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity. These results suggest that the intracellular domain, but not the ligand binding domain, of Dectin-1 modulate their functions which determine the ligand spectrum.
2017-08-25 | GSE98814 | GEO
Project description:Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity
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