PMID- 22999859
OWN - NLM
STAT- MEDLINE
DCOM- 20130312
LR  - 20220408
IS  - 1934-6069 (Electronic)
IS  - 1931-3128 (Print)
IS  - 1931-3128 (Linking)
VI  - 12
IP  - 4
DP  - 2012 Oct 18
TI  - Outer membrane vesicles of a human commensal mediate immune regulation and 
      disease protection.
PG  - 509-20
LID - S1931-3128(12)00275-2 [pii]
LID - 10.1016/j.chom.2012.08.004 [doi]
AB  - Commensal bacteria impact host health and immunity through various mechanisms, 
      including the production of immunomodulatory molecules. Bacteroides fragilis 
      produces a capsular polysaccharide (PSA), which induces regulatory T cells and 
      mucosal tolerance. However, unlike pathogens, which employ secretion systems, the 
      mechanisms by which commensal bacteria deliver molecules to the host remain 
      unknown. We reveal that Bacteroides fragilis releases PSA in outer membrane 
      vesicles (OMVs) that induce immunomodulatory effects and prevent experimental 
      colitis. Dendritic cells (DCs) sense OMV-associated PSA through TLR2, resulting 
      in enhanced regulatory T cells and anti-inflammatory cytokine production. 
      OMV-induced signaling in DCs requires growth arrest and DNA-damage-inducible 
      protein (Gadd45alpha). DCs treated with PSA-containing OMVs prevent experimental 
      colitis, whereas Gadd45alpha(-/-) DCs are unable to promote regulatory T cell 
      responses or suppress proinflammatory cytokine production and host pathology. 
      These findings demonstrate that OMV-mediated delivery of a commensal molecule 
      prevents disease, uncovering a mechanism of interkingdom communication between 
      the microbiota and mammals.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Shen, Yue
AU  - Shen Y
AD  - Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
FAU - Giardino Torchia, Maria Letizia
AU  - Giardino Torchia ML
FAU - Lawson, Gregory W
AU  - Lawson GW
FAU - Karp, Christopher L
AU  - Karp CL
FAU - Ashwell, Jonathan D
AU  - Ashwell JD
FAU - Mazmanian, Sarkis K
AU  - Mazmanian SK
LA  - eng
SI  - GEO/GSE39563
GR  - GM007616/GM/NIGMS NIH HHS/United States
GR  - T32 GM007616/GM/NIGMS NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - R21 DK083633/DK/NIDDK NIH HHS/United States
GR  - DK078938/DK/NIDDK NIH HHS/United States
GR  - R01 DK078938/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120920
PL  - United States
TA  - Cell Host Microbe
JT  - Cell host & microbe
JID - 101302316
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Gadd45a protein, mouse)
RN  - 0 (Immunologic Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Polysaccharides, Bacterial)
RN  - 0 (Toll-Like Receptor 2)
SB  - IM
CIN - Cell Host Microbe. 2012 Oct 18;12(4):392-3. PMID: 23084908
MH  - Animals
MH  - Bacteroides fragilis/*immunology/*metabolism
MH  - Cell Cycle Proteins/genetics/immunology
MH  - Cytokines/metabolism
MH  - Dendritic Cells/drug effects/immunology
MH  - Exosomes/*immunology/*metabolism
MH  - Gene Expression Profiling
MH  - Immunologic Factors/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nuclear Proteins/genetics/immunology
MH  - Polysaccharides, Bacterial/immunology/*metabolism
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Toll-Like Receptor 2/drug effects/immunology
PMC - PMC3895402
MID - NIHMS404287
EDAT- 2012/09/25 06:00
MHDA- 2013/03/13 06:00
PMCR- 2014/01/18
CRDT- 2012/09/25 06:00
PHST- 2012/03/03 00:00 [received]
PHST- 2012/06/08 00:00 [revised]
PHST- 2012/08/01 00:00 [accepted]
PHST- 2012/09/25 06:00 [entrez]
PHST- 2012/09/25 06:00 [pubmed]
PHST- 2013/03/13 06:00 [medline]
PHST- 2014/01/18 00:00 [pmc-release]
AID - S1931-3128(12)00275-2 [pii]
AID - 10.1016/j.chom.2012.08.004 [doi]
PST - ppublish
SO  - Cell Host Microbe. 2012 Oct 18;12(4):509-20. doi: 10.1016/j.chom.2012.08.004. 
      Epub 2012 Sep 20.