Outer Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection

By Yue Shen, Maria Letizia Giardino Torchia, G. Lawson, C. Karp, J. Ashwell, S. Mazmanian. Cell Host and Microbe, 2012

677 citations recorded by the source corpus.

Summary 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 pro-inflammatory cytokine production and host pathology. These findings demonstrate that OMV-mediated delivery of a commensal molecule prevents disease, uncovering a mechanism of inter-kingdom communication between the microbiota and mammals.

Subfields: Epidemiology, Microbiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9c14b03cb61a2891bf1dfa60b43ed0b05f5cd7d5

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. V. Gopalakrishnan
2. Beth A. Helmink
3. J. Wargo

Citations in the corpus

• Homeostatic immunity and the microbiota (2017, neutral): “, 2001) but could also result from capture of microbial outer membrane vesicles (OMVs) (Shen et al., 2012).”
• Bacterial outer membrane vesicles mediate cytosolic localization of LPS and caspase-11 activation (2016, neutral): “Furthermore, OMVs produced by gut microbiota play an immunomodulatory role in mucosal immunity (Hickey et al., 2015; Shen et al., 2012).”
• The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. (2018, background): “In addition, some bacterial species have been shown to drive Treg development via alternative pathways dependent on polysaccharide A and TLR signaling to DCs (Round and Mazmanian, 2010; Shen et al., 2012).”
• Gut Bacteroides species in health and disease (2021, neutral): “PSA is packaged into OMVs and delivered to host cells.(160)”