Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity

Tomotsugu Takano, Chihiro Motozono, Takashi Imai, Koh Hei Sonoda, Yoichi Nakanishi, Sho Yamasaki

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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 Dec-tin-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 -glu-can 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 -glu-can 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.

Original languageEnglish
Pages (from-to)16933-16941
Number of pages9
JournalJournal of Biological Chemistry
Volume292
Issue number41
DOIs
Publication statusPublished - Oct 13 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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