AUTHOR=Martin-Gallausiaux Camille , Malabirade Antoine , Habier Janine , Wilmes Paul 

TITLE=Fusobacterium nucleatum Extracellular Vesicles Modulate Gut Epithelial Cell Innate Immunity via FomA and TLR2

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.583644

DOI=10.3389/fimmu.2020.583644

ISSN=1664-3224

ABSTRACT=<p>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 <italic>F. nucleatum</italic> 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 <italic>F. nucleatum</italic> EVs trigger innate immunity of IECs by promoting NF-κB activation <italic>via</italic> 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 <italic>F. nucleatum</italic> bacteria on IECs. In particular, our study highlights the role of TLR2 and FomA as major modulators of the gut epithelium immune responses to <italic>F. nucleatum</italic>.</p>