A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response.
Charles S FermainttKanae SanoZhida LiuNozomi IshiiJunichi SeinoNicole DobbsTadashi SuzukiYang-Xin FuMark A LehrmanIchiro MatsuoNan YanPublished in: Nature communications (2019)
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.
Keyphrases
- immune response
- innate immune
- dendritic cells
- toll like receptor
- cell surface
- ms ms
- multiple sclerosis
- microbial community
- genome wide
- mass spectrometry
- candida albicans
- dna methylation
- ultrasound guided
- gram negative
- high performance liquid chromatography
- hepatitis c virus
- hiv testing
- deep learning
- multidrug resistant
- antimicrobial resistance
- men who have sex with men