Abstract
BackgroundBacteroides 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).ResultsIn healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression 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 a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. 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).ConclusionsOverall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients.A3C6cuutcZR_V1iQMS6TL7Video
Highlights
The human gastrointestinal (GI) tract contains an estimated 3.8 × 1013 bacteria (1011/mL contents) that play an essential role in digestion, pathogen resistance and the development of different sensory systems within the GI tract including the immune system [1,2,3]
In order to examine mucosal immune responses to outer membrane vesicles (OMVs), colonic biopsies from healthy individuals were cultured intact in a polarised in vitro culture system for 6 h with 108-109 Bacteroides thetaiotaomicron (Bt) OMVs/mlor medium alone added to the apical surface
To determine if dendritic cells (DC) were a source of cytokines in the polarised in vitro culture system (pIVOC) system, total lamina propria (LP) cells were obtained from five distal and five proximal colonic biopsies by enzymatic digestion and were cultured for 20 h in the presence of either non-viable Bt (107 cfu/mL), Bt
Summary
The human gastrointestinal (GI) tract contains an estimated 3.8 × 1013 bacteria (1011/mL contents) that play an essential role in digestion, pathogen resistance and the development of different sensory systems within the GI tract including the immune system [1,2,3]. Gramnegative Bacteroides thetaiotaomicron (Bt) is a prominent member of the intestinal microbiota of many animals [4,5,6]. Typical of all gram-negative bacteria, Bt generates nanosized outer membrane vesicles (OMVs) during its normal growth [12, 13]. 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. 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)
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