Dataset Information

Membrane Vesicles of a Bacterial Mutualist Mediate Immune Regulation via Dendritic Cells

ABSTRACT: Microbial molecules have evolved to promote transient and/or permanent associations with mammals. Although numerous examples of secretion systems employed by pathogens have been described, mechanisms by which commensal bacteria export molecules during symbiosis remain unknown. The human gut mutualist Bacteroides fragilis produces a capsular polysaccharide (PSA) that directs host immune development. We reveal herein that outer membrane vesicles (OMVs) deliver PSA to dendritic cells (DCs), promoting regulatory T cells and inducing anti-inflammatory cytokines during protection from intestinal disease. In addition, we found that TLR2 signaling by DCs is required for OMV sensing. Following internalization into DCs and engagement of TLR2, OMVs initiate a gene expression program that results in IL-10 production by DCs. Although it is known that the outcome of PSA sensing by the immune system is Treg induction, nothing is known about the intracellular signaling pathway(s) activated by PSA within DCs. We analyzed the gene expression profile of DCs treated with OMVs to uncover factors that are expressed in a PSA-dependent, TLR2-dependent manner. Our findings demonstrate DC-induced protection from disease via OMV-delivery of a beneficial microbial molecule, uncovering a novel paradigm for inter-kingdom communication between the microbiota and mammals.

ORGANISM(S): Mus musculus

PROVIDER: GSE39563 | GEO | 2012/07/23

SECONDARY ACCESSION(S): PRJNA171137

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:. The transition of the opportunistic pathogen Pseudomonas aeruginosa from free-living bacteria into surface-associated biofilm communities represents a viable target for the prevention and treatment of chronic infectious disease. We have established a proteomics platform that identified 2443 and 1142 high-confidence proteins in P. aeruginosa whole cells and outer membrane vesicles (OMVs), respectively, at three time points during biofilm development. Analysis of cellular systems, specifically the phenazine biosynthetic pathway, demonstrates that whole cell protein abundance correlates to end product (i.e., pyocyanin) concentrations in biofilm but not planktonic cultures. Furthermore, increased cellular protein abundance in this pathway results in quantifiable pyocyanin in early biofilm OMVs, and OMVs from both growth modes isolated at later time points. Overall, our data indicate that the OMVs being released from the surface of the biofilm whole cells have unique proteomes in comparison to their planktonic counterparts. The relative abundance of OMV proteins from various subcellular sources showed considerable differences between the two growth modes over time, supporting the existence and preferential activation of multiple OMV biogenesis mechanisms under different conditions. The consistent detection of cytoplasmic proteins in the OMV subproteome suggests that these proteins may contribute a small but functionally relevant component to biofilm OMVs. Direct comparisons of outer membrane protein abundance levels between OMVs and whole cells shows ratios that vary greatly from 1:1, and supports previous studies that advocate specific inclusion, or “packaging”, of proteins into OMVs. The detailed analysis of packaged protein groups indicates biogenesis mechanisms that involve untethered, rather than absent, peptidoglycan-binding proteins. Collectively, individual protein and biological system analyses of biofilm OMVs show that drug-binding cytoplasmic proteins and porins are shuttled from the whole cell into the OMVs, potentially contributing to the antibiotic resistance of P. aeruginosa whole cells within biofilms.

Dataset Information

Membrane Vesicles of a Bacterial Mutualist Mediate Immune Regulation via Dendritic Cells

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure