Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease

Durant L., Stentz R., Noble A., Brooks J., Gicheva N., Reddi D., OConnor M., Hoyles L., McCartney A. L., Man R., Tobias Pring E., Dilke S., Hendy P., Segal J., Lim D., Misra R., Hart A. L., Arebi N., Carding S. R., Knight S.. (2020)

Microbiome, 8, Microbiome volume 8, Article number: 88 (2020)

Background
Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that like all Gram-negative bacteria naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn’s disease (CD) or ulcerative colitis (UC).
Results
In healthy individuals, Bt OMVs stimulated significant IL-10 expression (p<0.05) by colonic DC whereas in peripheral blood-derived DC they also stimulated significant expression of IL-6 (p<0.0001) and the activation marker CD80 (p<0.001). Conversely, in UC Bt OMVs were unable to elicit IL-10 production by colonic DC. There were also reduced numbers of CD103+ DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited significantly less IL-10 from blood DC compared to controls (p<0.01; p<0.001, respectively). These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD).
Conclusions
Overall, our findings suggest a key role for OMVs generated by commensal gut bacteria in directing a balanced immune response to the microbiota both locally and systemically during health which is altered in the context of gastrointestinal disease in IBD patients.
 

Microbiome, 8, Microbiome volume 8, Article number: 88 (2020)

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