[en] Extracellular vesicles (EVs) derived from the gut microbiota are largely uncharacterized and their impacts on host intestinal physiology remain unresolved. Here, we isolated EVs from F. nucleatum for detailed characterization. Our analyses highlight the presence of the outer membrane protein porin FomA on EVs. Besides, we evaluated the impact of EVs on human intestinal epithelial cells (IECs) in a non-inflammatory context. Our results show no detrimental impact on the epithelial barrier. No internalization of EVs was observed. Moreover, we demonstrate that F. nucleatum EVs trigger innate immunity of IECs by promoting NF-κB activation via the dynamin-mediated endocytosis. The NF-κB activation was found to be TLR2-dependent yet, TLR4 was dispensable. Using competitive binding assays, we establish that FomA is involved in the NF-κB response. Taken together, our data indicate that EVs induce effects similar to those observed with whole F. nucleatum bacteria on IECs. In particular, our study highlights the role of TLR2 and FomA as major modulators of the gut epithelium immune responses to F. nucleatum.
Disciplines :
Microbiology
Author, co-author :
MARTIN-GALLAUSIAUX, Camille ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Systems Ecology > Team Paul WILMES
FNR10404093 - Non-invasive Microbiome-derived Multi-omic Biomarkers For Early-stage Colorectal Cancer Detection, 2015 (01/01/2016-30/04/2019) - Paul Wilmes
Funders :
Fonds National de la Recherche Luxembourg
Funding text :
We thank O. Lecha and G. Walbrecq (University of Luxembourg, LSR) for using the NanoSight device. We also acknowledge the support and the use of resources of the French Infrastructure for Integrated Structural Biology FRISBI ANR-10-INBS-05 and of Instruct-ERIC for TEM imaging, and particularly Corinne Crucifix.This work was supported by the Luxembourg National Research Fund (FNR) Microcancer grant (CORE/15/BM/10404093) and Bilateral FNR grant (AFR Bilateral/11228353-4).
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