A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response
| Autor: | Ichiro Matsuo, Nan Yan, Junichi Seino, Mark A. Lehrman, Kanae Sano, Nozomi Ishii, Zhida Liu, Charles S. Fermaintt, Tadashi Suzuki, Nicole Dobbs, Yang Xin Fu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Autoimmune diseases animal diseases Glycobiology Disaccharide General Physics and Astronomy Autoimmunity 02 engineering and technology Disaccharides Endoplasmic Reticulum medicine.disease_cause Mice chemistry.chemical_compound lcsh:Science Multidisciplinary biology 021001 nanoscience & nanotechnology 3. Good health Cell biology 0210 nano-technology Glycan Science chemical and pharmacologic phenomena Protein Serine-Threonine Kinases Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immune system Immunity medicine Animals Autoimmune disease Innate immune system Oligosaccharyltransferase Membrane Proteins General Chemistry Fibroblasts biochemical phenomena metabolism and nutrition Phosphoproteins medicine.disease Immunity Innate Disease Models Animal Exodeoxyribonucleases RAW 264.7 Cells 030104 developmental biology chemistry biology.protein bacteria lcsh:Q |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-10319-5 |
| Popis: | Glycans from microbial pathogens are well known pathogen-associated molecular patterns that are recognized by the host immunity; however, little is known about whether and how mammalian self-glycans activate the host immune response, especially in the context of autoimmune disease. Using biochemical fractionation and two-dimensional HPLC, we identify an abundant and bioactive free glycan, the Manβ1-4GlcNAc disaccharide in TREX1-associated autoimmune diseases. We report that both monosaccharide residues and the β1-4 linkage are critical for bioactivity of this disaccharide. We also show that Manβ1-4GlcNAc is produced by oligosaccharyltransferase hydrolysis of lipid-linked oligosaccharides in the ER lumen, followed by ENGase and mannosidase processing in the cytosol and lysosomes. Furthermore, synthetic Manβ1-4GlcNAc disaccharide stimulates a broad immune response in vitro, which is in part dependent on the STING-TBK1 pathway, and enhances antibody response in vivo. Together, our data identify Manβ1-4GlcNAc as a novel innate immune modulator associated with chronic autoimmune diseases. Mammalian glycans have a role in host immunity but little is known about how they activate the host response in the context of autoimmune diseases. Here, the authors identify Manβ1-4GlcNAc as a novel innate immune modulator associated with chronic autoimmune diseases. |
| Databáze: | OpenAIRE |
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