1. Regulating colonic dendritic cells by commensal glycosylated large surface layer protein A to sustain gut homeostasis against pathogenic inflammation
- Author
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Nitin T. Supekar, Laurence Morel, Roberto Sonon, Jeffrey R. Abbott, Dean P. Jones, Wei Li, Mansour Mohamadzadeh, Shuzhao Li, Mojgan Zadeh, Parastoo Azadi, Yong Ge, Jing Li, Yating Wang, and Minghao Gong
- Subjects
0301 basic medicine ,colitis ,T-Lymphocytes ,Lymphocyte Activation ,Transcriptome ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,intestinal inflammation ,Immunology and Allergy ,Listeriosis ,Phagocytic Cell ,Receptor ,S-layer glycosylation ,Cells, Cultured ,Mice, Knockout ,biology ,Cell Differentiation ,Cell biology ,medicine.symptom ,Protein Binding ,Glycosylation ,Colon ,Listeria ,Immunology ,Receptors, Cell Surface ,Inflammation ,Listeria infection ,Article ,Proinflammatory cytokine ,03 medical and health sciences ,Bacterial Proteins ,medicine ,Animals ,Humans ,colonic DCs ,Lectins, C-Type ,Symbiosis ,immune regulation ,Propionibacterium ,Dendritic Cells ,Inflammatory Bowel Diseases ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,biology.protein ,Protein A ,Cell Adhesion Molecules ,030215 immunology - Abstract
Microbial interaction with the host through sensing receptors, including SIGNR1, sustains intestinal homeostasis against pathogenic inflammation. The newly discovered commensal Propionibacterium strain, P. UF1, regulates the intestinal immunity against pathogen challenge. However, the molecular events driving intestinal phagocytic cell response, including colonic dendritic cells (DCs), by this bacterium are still elusive. Here, we demonstrate that the glycosylation of bacterial large surface layer protein A (LspA) by protein O-mannosyltransferase 1 (Pmt1) regulates the interaction with SIGNR1, resulting in the control of DC transcriptomic and metabolomic machineries. Programmed DCs promote protective T cell response to intestinal Listeria infection and resist chemically induced colitis in mice. Thus, our findings may highlight a novel molecular mechanism by which commensal surface glycosylation interacting with SIGNR1 directs the intestinal homeostasis to potentially protect the host against proinflammatory signals inducing colonic tissue damage.
- Published
- 2020
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