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Beneficial bacteria activate type-I interferon production via the intracellular cytosolic sensors STING and MAVS

Gutierrez, Jorge, Isla, Beatriz, Combes, Theo, Martinez Estrada, Fernando Oneissi and Maluquer de Motes, Carlos (2019) Beneficial bacteria activate type-I interferon production via the intracellular cytosolic sensors STING and MAVS Gut Microbes.

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Abstract

Type-I interferon (IFN-I) cytokines are produced by immune cells in response to microbial infections, cancer and autoimmune diseases, and subsequently, trigger cytoprotective and antiviral responses through the activation of IFN-I stimulated genes (ISGs). The ability of intestinal microbiota to modulate innate immune responses is well known, but the mechanisms underlying such responses remain elusive. Here we report that the intracellular sensors stimulator of IFN genes (STING) and mitochondrial antiviral signaling (MAVS) are essential for the production of IFN-I in response to lactic acid bacteria (LAB), common gut commensal bacteria with beneficial properties. Using human macrophage cells we show that LAB strains that potently activate the inflammatory transcription factor NF-κB are poor inducers of IFN-I and conversely, those triggering significant amounts of IFN-I fail to activate NF-κB. This IFN-I response is also observed in human primary macrophages, which modulate CD64 and CD40 upon challenge with IFN-I-inducing LAB. Mechanistically, IFN-I inducers interact more intimately with phagocytes as compared to NF-κB-inducers, and fail to activate IFN-I in the presence of phagocytosis inhibitors. These bacteria are then sensed intracellularly by the cytoplasmic sensors STING and, to a lesser extent, MAVS. Accordingly, macrophages deficient for STING showed dramatically reduced phosphorylation of TANK-binding kinase (TBK)-1 and IFN-I activation, which resulted in lower expression of ISGs. Our findings demonstrate a major role for intracellular sensing and STING in the production of IFN-I by beneficial bacteria and the existence of bacteria-specific immune signatures, which can be exploited to promote cytoprotective responses and prevent overreactive NF-κB-dependent inflammation in the gut.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Gutierrez, Jorgej.gutierrez@surrey.ac.uk
Isla, Beatriz
Combes, Theot.combes@surrey.ac.uk
Martinez Estrada, Fernando Oneissif.martinezestrada@surrey.ac.uk
Maluquer de Motes, Carlosc.maluquerdemotes@surrey.ac.uk
Date : 10 December 2019
Funders : BBRSC
OA Location : https://www.tandfonline.com/doi/full/10.1080/19490976.2019.1707015
Grant Title : BBSRC Grant
Copyright Disclaimer : © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
Uncontrolled Keywords : Lactic acid bacteria, beneficial microbes, interferon, STING, MAVS
Depositing User : James Marshall
Date Deposited : 04 Feb 2020 13:21
Last Modified : 05 Feb 2020 09:45
URI: http://epubs.surrey.ac.uk/id/eprint/853642

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