Outer membrane vesicles of a human commensal mediate immune regulation and disease protection

Cell Host Microbe. 2012 Oct 18;12(4):509-20. doi: 10.1016/j.chom.2012.08.004. Epub 2012 Sep 20.


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 (Gadd45α). DCs treated with PSA-containing OMVs prevent experimental colitis, whereas Gadd45α(-/-) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroides fragilis / immunology*
  • Bacteroides fragilis / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Exosomes / immunology*
  • Exosomes / metabolism*
  • Gene Expression Profiling
  • Immunologic Factors / immunology
  • Immunologic Factors / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology
  • Polysaccharides, Bacterial / immunology
  • Polysaccharides, Bacterial / metabolism*
  • T-Lymphocytes, Regulatory / immunology
  • Toll-Like Receptor 2 / drug effects
  • Toll-Like Receptor 2 / immunology


  • Cell Cycle Proteins
  • Cytokines
  • Gadd45a protein, mouse
  • Immunologic Factors
  • Nuclear Proteins
  • Polysaccharides, Bacterial
  • Toll-Like Receptor 2

Associated data

  • GEO/GSE39563