University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Beneficial bacteria activate type-I interferon production via the 1 intracellular cytosolic sensors STING and MAVS

Gutierrez-Merino, Jorge, Isla, Beatriz, Combes, Theo, Martinez-Estrada, Fernando and Maluquer de Motes, Carlos (2020) Beneficial bacteria activate type-I interferon production via the 1 intracellular cytosolic sensors STING and MAVS Gut Microbes.

[img] Text
Gutierrez-Merino et al 2019_Gut Microbes_Revised.pdf - Accepted version Manuscript
Restricted to Repository staff only until 16 January 2021.

Download (411kB)

Abstract

Type-I interferon (IFN-I) cytokines are produced by immune cells in response to microbial infections, 2cancer 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 signalling (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-Merino, Jorge
Isla, Beatriz
Combes, Theot.combes@surrey.ac.uk
Martinez-Estrada, Fernando
Maluquer de Motes, Carlosc.maluquerdemotes@surrey.ac.uk
Date : 15 January 2020
Funders : Biotechnology and Biological Science Research Council (BBSRC)
DOI : 10.1080/19490976.2019.1707015
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 : Diane Maxfield
Date Deposited : 13 Dec 2019 10:50
Last Modified : 27 Apr 2020 10:21
URI: http://epubs.surrey.ac.uk/id/eprint/853253

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800