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

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Title: Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease
Authors: Durant, L
Stentz, R
Noble, A
Reddi, D
Brooks, J
Gicheva, N
O'Connor, MJ
Hoyles, L
McCartney, AL
Man, R
Pring, ET
Dilke, S
Hendy, P
Segal, JP
Lim, DNF
Misra, R
Hart, AL
Arebi, N
Carding, SR
Knight, SC
Item Type: Journal Article
Abstract: 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 (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). Conclusions Overall, 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.
Editors: Lapaque, N
Issue Date: 8-Jun-2020
Date of Acceptance: 11-May-2020
URI: http://hdl.handle.net/10044/1/80197
DOI: 10.1186/s40168-020-00868-z
ISSN: 2049-2618
Publisher: BioMed Central
Journal / Book Title: Microbiome
Volume: 8
Copyright Statement: © The Author(s). 2020. This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/.The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to thedata made available in this article, unless otherwise stated in a credit line to the data
Sponsor/Funder: Biotechnology and Biological Research Council (BBSRC)
Biotechnology and Biological Sciences Research Cou
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: BB/J004529/1
BB/R012490/1
MR/L01632X/1
MR/L01632X/1
Keywords: Bacteroides thetaiotaomicron
Dendritic cells
Inflammatory bowel disease
Interleukin-10
Outer membrane vesicles
Dendritic Cells
Bacteroides thetaiotaomicron
outer membrane vesicles
Inflammatory Bowel Diseases
Interleukin-10
0602 Ecology
0605 Microbiology
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN 88
Appears in Collections:Department of Surgery and Cancer
Department of Infectious Diseases
Faculty of Medicine
School of Public Health