| First Author | Wittmann A | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 34 | Pages | 17629-38 |
| PubMed ID | 27358401 | Mgi Jnum | J:291648 |
| Mgi Id | MGI:6204732 | Doi | 10.1074/jbc.M116.741256 |
| Citation | Wittmann A, et al. (2016) Dectin-2 Recognizes Mannosylated O-antigens of Human Opportunistic Pathogens and Augments Lipopolysaccharide Activation of Myeloid Cells. J Biol Chem 291(34):17629-38 |
| abstractText | LPS consists of a relatively conserved region of lipid A and core oligosaccharide and a highly variable region of O-antigen polysaccharide. Whereas lipid A is known to bind to the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear. Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin-2) and mannosylated O-antigen found in a human opportunistic pathogen, Hafnia alvei PCM 1223, which has a repeating unit of [-Man-alpha1,3-Man-alpha1,2-Man-alpha1,2-Man-alpha1,2-Man-alpha1,3-]. H. alvei LPS induced higher levels of TNFalpha and IL-10 from mouse bone marrow-derived dendritic cells (BM-DCs), when compared with Salmonella enterica O66 LPS, which has a repeat of [-Gal-alpha1,6-Gal-alpha1,4-[Glc-beta1,3]GalNAc-alpha1,3-GalNAc-beta1,3-]. In a cell-based reporter assay, Dectin-2 was shown to recognize H. alvei LPS. This binding was inhibited by mannosidase treatment of H. alvei LPS and by mutations in the carbohydrate-binding domain of Dectin-2, demonstrating that H. alvei LPS is a novel glycan ligand of Dectin-2. The enhanced cytokine production by H. alvei LPS was Dectin-2-dependent, because Dectin-2 knock-out BM-DCs failed to do so. This receptor cross-talk between Dectin-2 and TLR4 involved events including spleen tyrosine kinase (Syk) activation and receptor juxtaposition. Furthermore, another mannosylated LPS from Escherichia coli O9a also bound to Dectin-2 and augmented TLR4 activation of BM-DCs. Taken together, these data indicate that mannosylated O-antigens from several Gram-negative bacteria augment TLR4 responses through interaction with Dectin-2. |
