Extracellular vesicles produced by the human gut commensal bacterium Bacteroides thetaiotaomicron elicit anti-inflammatory responses from innate immune cells

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Fonseca, Sonia, Carvalho, Ana L., Miquel-Clopés, Ariadna, Jones, Emily J., Juodeikis, Rokas, Stentz, Régis and Carding, Simon R. (2022) Extracellular vesicles produced by the human gut commensal bacterium Bacteroides thetaiotaomicron elicit anti-inflammatory responses from innate immune cells. Frontiers in Microbiology, 13. ISSN 1664-302X

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Abstract

Bacterial extracellular vesicles (BEVs) produced by gut commensal bacteria have been proposed to play an important role in maintaining host homeostasis via interactions with the immune system. Details of the mediators and pathways of BEV-immune cell interactions are however incomplete. In this study, we provide evidence for the anti-inflammatory and immunomodulatory properties of extracellular vesicles produced by the prominent human gut commensal bacterium Bacteroides thetaiotaomicron (Bt BEVs) and identify the molecular mechanisms underlying their interaction with innate immune cells. Administration of Bt BEVs to mice treated with colitis-inducing dextran sodium sulfate (DSS) ameliorates the symptoms of intestinal inflammation, improving survival rate and reducing weight loss and disease activity index scores, in association with upregulation of IL-10 production in colonic tissue and in splenocytes. Pre-treatment (conditioning) of murine bone marrow derived monocytes (BMDM) with Bt BEVs resulted in higher ratio of IL-10/TNFα production after an LPS challenge when compared to LPS pre-conditioned or non-conditioned BMDM. Using the THP-1 monocytic cell line the interactions between Bt BEVs and monocytes/macrophages were shown to be mediated primarily by TLR2. Histone (H3K4me1) methylation analysis showed that Bt BEVs induced epigenetic reprogramming which persisted after infectious challenge, as revealed by increased levels of H3K4me1 in Bt BEV-conditioned LPS-challenged BMDM. Collectively, our findings highlight the important role of Bt BEVs in maintaining host immune homeostasis and raise the promising possibility of considering their use in immune therapies.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Related URLs:	https://www.frontiersin.org/articles/10....
Depositing User:	LivePure Connector
Date Deposited:	19 Dec 2022 17:32
Last Modified:	14 Jun 2023 14:12
URI:	https://ueaeprints.uea.ac.uk/id/eprint/90309
DOI:	10.3389/fmicb.2022.1050271

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