Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell‐type specific manner that are altered in inflammatory bowel disease

• Published in: Journal of extracellular vesicles Vol. 11; no. 1; pp. e12189 - n/a
• Main Authors: Gul, Lejla, Modos, Dezso, Fonseca, Sonia, Madgwick, Matthew, Thomas, John P., Sudhakar, Padhmanand, Booth, Catherine, Stentz, Régis, Carding, Simon R., Korcsmaros, Tamas
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2022; John Wiley and Sons Inc; Wiley
• Subjects: Adaptor proteins; Antigens; Bacteria; Bacterial vesicles; Bacteroides thetaiotaomicron; Bacteroides thetaiotaomicron - metabolism; Cell activation; Cell differentiation; Cell interactions; Chromatography; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Digestive system; E coli; Extracellular vesicles; Extracellular Vesicles - metabolism; Gastrointestinal Microbiome - immunology; Gastrointestinal tract; Gram-negative bacteria; Gram-positive bacteria; Homeostasis; Host Microbial Interactions; host‐microbe interactions; Humans; Immune system; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - microbiology; Intestine; Lipids; Macrophages; Macrophages - immunology; Macrophages - metabolism; Membrane Glycoproteins - antagonists & inhibitors; Microbiomes; Microbiota; Microorganisms; Molecular weight; Monocytes; Monocytes - immunology; Monocytes - metabolism; Peptides; Protein Interaction Maps; Proteins; Proteomics; Receptors, Interleukin-1 - antagonists & inhibitors; Signal Transduction; single‐cell data analysis; TLR4 protein; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-like receptors; Toll-Like Receptors - metabolism; toll‐like receptor pathway; Ulcerative colitis; United Kingdom > UK; host-microbe interactions; ulcerative colitis; extracellular vesicles; single-cell data analysis; toll-like receptor pathway
• ISSN: 2001-3078; 2001-3078
• DOI: 10.1002/jev2.12189

The gastrointestinal (GI) tract harbours a complex microbial community, which contributes to its homeostasis. A disrupted microbiome can cause GI‐related diseases, including inflammatory bowel disease (IBD), therefore identifying host‐microbe interactions is crucial for better understanding gut health. Bacterial extracellular vesicles (BEVs), released into the gut lumen, can cross the mucus layer and access underlying immune cells. To study BEV‐host interactions, we examined the influence of BEVs generated by the gut commensal bacterium, Bacteroides thetaiotaomicron, on host immune cells. Single‐cell RNA sequencing data and host‐microbe protein‐protein interaction networks were used to predict the effect of BEVs on dendritic cells, macrophages and monocytes focusing on the Toll‐like receptor (TLR) pathway. We identified biological processes affected in each immune cell type and cell‐type specific processes including myeloid cell differentiation. TLR pathway analysis highlighted that BEV targets differ among cells and between the same cells in healthy versus disease (ulcerative colitis) conditions. The in silico findings were validated in BEV‐monocyte co‐cultures demonstrating the requirement for TLR4 and Toll‐interleukin‐1 receptor domain‐containing adaptor protein (TIRAP) in BEV‐elicited NF‐kB activation. This study demonstrates that both cell‐type and health status influence BEV‐host communication. The results and the pipeline could facilitate BEV‐based therapies for the treatment of IBD.