Extracellular vesicles produced by the human commensal gutbacteriumBacteroides thetaiotaomicronaffect host immunepathways in a cell-type specific manner that are altered ininflammatory bowel disease

Gul LEJLA, Modos DEZSO, Fonseca SONIA, Madgwick M, Thomas J, Sudhakar P, Booth C, Stentz R, Carding S, Korcsmaros . (2022)

Journal of Extracellular Vesicles

The gastrointestinal (GI) tract harbours a complex microbial community, which con-tributes to its homeostasis. A disrupted microbiome can cause GI-related diseases,including inflammatory bowel disease (IBD), therefore identifying host-microbeinteractions is crucial for better understanding gut health. Bacterial extracellularvesicles (BEVs), released into the gut lumen, can cross the mucus layer and accessunderlying immune cells. To study BEV-host interactions, we examined the influenceof 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 dendriticcells, macrophages and monocytes focusing on the Toll-like receptor (TLR) pathway.We identified biological processes affected in each immune cell type and cell-typespecific processes including myeloid cell differentiation. TLR pathway analysis high-lighted that BEV targets differ among cells and between the same cells in healthy ver-sus disease (ulcerative colitis) conditions. Thein silicofindings 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 acti-vation. This study demonstrates that both cell-type and health status influence BEV-host communication. The results and the pipeline could facilitate BEV-based thera-pies for the treatment of IBD

Journal of Extracellular Vesicles

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