Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease.
Bacteroides thetaiotaomicron
Dendritic cells
Inflammatory bowel disease
Interleukin-10
Outer membrane vesicles
Journal
Microbiome
ISSN: 2049-2618
Titre abrégé: Microbiome
Pays: England
ID NLM: 101615147
Informations de publication
Date de publication:
08 06 2020
08 06 2020
Historique:
received:
17
12
2019
accepted:
13
05
2020
entrez:
10
6
2020
pubmed:
10
6
2020
medline:
2
3
2021
Statut:
epublish
Résumé
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). 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 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. Video Abstract.
Sections du résumé
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
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. Video Abstract.
Identifiants
pubmed: 32513301
doi: 10.1186/s40168-020-00868-z
pii: 10.1186/s40168-020-00868-z
pmc: PMC7282036
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
88Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L004291/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J004529/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R012490/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/000PR10353
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/000PR10356
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L01632X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/000PR10355
Pays : United Kingdom
Références
Biochem Soc Trans. 2018 Oct 19;46(5):1021-1027
pubmed: 30154095
mBio. 2018 Mar 13;9(2):
pubmed: 29535205
Nat Immunol. 2014 Jan;15(1):98-108
pubmed: 24292363
J Exp Med. 2020 Jan 6;217(1):
pubmed: 31611251
mBio. 2014 Mar 11;5(2):e00909-14
pubmed: 24618254
Cell Mol Gastroenterol Hepatol. 2015 Sep 03;2(1):22-39.e5
pubmed: 26866054
J Exp Med. 1991 Nov 1;174(5):1209-20
pubmed: 1940799
Sci Rep. 2016 Apr 27;6:24866
pubmed: 27117743
Inflamm Bowel Dis. 2018 Mar 19;24(4):792-805
pubmed: 29529198
Inflamm Bowel Dis. 2014 Dec;20(12):2299-307
pubmed: 25397892
Nature. 2012 Jun 13;486(7402):207-14
pubmed: 22699609
Exp Biol Med (Maywood). 2012 May;237(5):540-7
pubmed: 22569032
Immunology. 2015 Feb;144(2):333-42
pubmed: 25179236
Clin Exp Immunol. 2019 Jun;196(3):287-304
pubmed: 30985006
Appl Microbiol. 1974 May;27(5):961-79
pubmed: 4598229
Cell Microbiol. 2009 Mar;11(3):521-30
pubmed: 19134113
Best Pract Res Clin Gastroenterol. 2004 Apr;18(2):255-70
pubmed: 15123068
Inflamm Bowel Dis. 2019 May 4;25(6):e71
pubmed: 30561647
Immunity. 2014 May 15;40(5):720-33
pubmed: 24792913
PeerJ. 2015 Jul 28;3:e1061
pubmed: 26246963
Mol Nutr Food Res. 2014 May;58(5):1132-43
pubmed: 24347371
J Pathol. 1999 Jun;188(2):220-6
pubmed: 10398168
Cell Host Microbe. 2015 May 13;17(5):672-80
pubmed: 25974305
Science. 2003 Mar 28;299(5615):2074-6
pubmed: 12663928
Cell Host Microbe. 2012 Oct 18;12(4):509-20
pubmed: 22999859
Eur J Immunol. 2012 May;42(5):1337-53
pubmed: 22539302
Cold Spring Harb Perspect Biol. 2014 Sep 04;6(10):a016295
pubmed: 25190079
Nat Immunol. 2004 Jan;5(1):104-12
pubmed: 14691478
Immunology. 2017 Aug;151(4):363-374
pubmed: 28542929
Gastroenterology. 2017 Nov;153(5):1320-1337.e16
pubmed: 28782508
Immunol Lett. 2013 Feb;150(1-2):30-40
pubmed: 23352670
J Exp Med. 1998 Feb 16;187(4):571-8
pubmed: 9463407
J Exp Med. 2007 Aug 6;204(8):1775-85
pubmed: 17620362
Am J Gastroenterol. 2011 Aug;106(8):1544-55
pubmed: 21519361
Eur J Immunol. 1997 May;27(5):1229-35
pubmed: 9174615
Vaccine. 2005 Mar 18;23(17-18):2191-6
pubmed: 15755593
Mucosal Immunol. 2016 Jan;9(1):171-82
pubmed: 26080709
Microbiology. 2015 Mar;161(Pt 3):565-79
pubmed: 25533445
Science. 2001 Feb 2;291(5505):881-4
pubmed: 11157169
BMC Biol. 2013 May 21;11:61
pubmed: 23692866
Biochem J. 2017 May 16;474(11):1823-1836
pubmed: 28512250
N Engl J Med. 2009 Nov 19;361(21):2033-45
pubmed: 19890111
Inflamm Bowel Dis. 2019 Jan 1;25(1):85-96
pubmed: 30215718
Front Microbiol. 2017 Dec 08;8:2440
pubmed: 29276507
Front Microbiol. 2020 Feb 06;11:57
pubmed: 32117106
J Exp Med. 1973 Nov 1;138(5):1156-67
pubmed: 4200775
J Crohns Colitis. 2020 May 21;14(4):525-537
pubmed: 31665283
Cell. 1993 Oct 22;75(2):263-74
pubmed: 8402911
J Immunol. 1991 Dec 1;147(11):3815-22
pubmed: 1940369
Mediators Inflamm. 2013;2013:573576
pubmed: 23970814
Semin Immunol. 2014 Feb;26(1):75-9
pubmed: 24447345
Nat Rev Gastroenterol Hepatol. 2017 Oct;14(10):573-584
pubmed: 28743984
Microbiome. 2018 Apr 20;6(1):73
pubmed: 29678198
PLoS Biol. 2016 Aug 19;14(8):e1002533
pubmed: 27541692
Gut. 2016 Feb;65(2):256-70
pubmed: 25666191
J Exp Med. 1975 Feb 1;141(2):297-305
pubmed: 803544
Autoimmun Rev. 2014 Jan;13(1):3-10
pubmed: 23774107
Inflamm Bowel Dis. 2011 May;17(5):1201-8
pubmed: 21484962
Immunity. 2014 May 15;40(5):706-19
pubmed: 24792912
Immunity. 2011 Apr 22;34(4):554-65
pubmed: 21511184
J Exp Med. 2007 Aug 6;204(8):1757-64
pubmed: 17620361
Inflamm Bowel Dis. 2013 Dec;19(13):2820-8
pubmed: 24216686
J Extracell Vesicles. 2019 Jun 24;8(1):1632100
pubmed: 31275534
Cancer Immunol Res. 2014 Apr;2(4):288-94
pubmed: 24764575
Cell Rep. 2014 Feb 27;6(4):646-56
pubmed: 24529702
Lancet. 2018 Dec 23;390(10114):2769-2778
pubmed: 29050646
Oncotarget. 2016 May 31;7(22):32015-30
pubmed: 27027442
J Antimicrob Chemother. 2015 Mar;70(3):701-9
pubmed: 25433011
Science. 2005 Jun 10;308(5728):1635-8
pubmed: 15831718
Mucosal Immunol. 2019 Sep;12(5):1201-1211
pubmed: 31417161
Biotechnol Adv. 2017 Sep;35(5):565-574
pubmed: 28522212
Gastroenterology. 2011 Aug;141(2):653-62, 662.e1-4
pubmed: 21679711
Am J Clin Nutr. 1972 Dec;25(12):1292-4
pubmed: 4639749
Nat Rev Immunol. 2015 Jun;15(6):375-87
pubmed: 25976515
Cell Host Microbe. 2011 May 19;9(5):390-403
pubmed: 21575910
J Gen Microbiol. 1967 Oct;49(1):1-11
pubmed: 4168882
J Exp Med. 2016 Apr 4;213(4):517-34
pubmed: 27001748