Intracellular bacteria engage a STING-TBK1-MVB12b pathway to enable paracrine cGAS-STING signalling

Nature Microbiology
Ramya NandakumarSøren R Paludan

Abstract

The innate immune system is crucial for eventual control of infections, but may also contribute to pathology. Listeria monocytogenes is an intracellular Gram-positive bacteria and a major cause of food-borne disease. However, important knowledge on the interactions between L. monocytogenes and the immune system is still missing. Here, we report that Listeria DNA is sorted into extracellular vesicles (EVs) in infected cells and delivered to bystander cells to stimulate the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway. This was also observed during infections with Francisella tularensis and Legionella pneumophila. We identify the multivesicular body protein MVB12b as a target for TANK-binding kinase 1 phosphorylation, which is essential for the sorting of DNA into EVs and stimulation of bystander cells. EVs from Listeria-infected cells inhibited T-cell proliferation, and primed T cells for apoptosis. Collectively, we describe a pathway for EV-mediated delivery of foreign DNA to bystander cells, and suggest that intracellular bacteria exploit this pathway to impair antibacterial defence.

References

Sep 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian T Edelson, Emil R Unanue
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Silvia StockingerThomas Decker
Aug 11, 2004·The Journal of Experimental Medicine·Victoria AuerbuchDaniel A Portnoy
Aug 11, 2004·The Journal of Experimental Medicine·Javier A CarreroEmil R Unanue
Aug 11, 2004·The Journal of Experimental Medicine·Ryan M O'ConnellGenhong Cheng
Aug 30, 2005·Nature Immunology·Taro KawaiShizuo Akira
Mar 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·David S WeissDenise M Monack
Jan 30, 2008·Current Protocols in Cell Biology·Clotilde ThéryAled Clayton
Mar 1, 2008·Science·Katarina TrajkovicMikael Simons
Feb 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thomas HenryDenise M Monack
Mar 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·D Michiel PegtelJaap M Middeldorp
Mar 25, 2010·European Journal of Immunology·Sarah KimVeit Hornung
Mar 31, 2010·Nature Immunology·Teresa Fernandes-AlnemriEmad S Alnemri
Apr 1, 2010·The Journal of Biological Chemistry·Nobuyoshi KosakaTakahiro Ochiya
Sep 29, 2011·Nature·Dara L BurdetteRussell E Vance
Oct 16, 2012·The EMBO Journal·Zeinab AbdullahPercy A Knolle
Jan 25, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristy A HoranSøren R Paludan
May 28, 2013·Immunity·Søren R Paludan, Andrew G Bowie
Feb 26, 2014·Nature Reviews. Immunology·Paul D Robbins, Adrian E Morelli
Apr 18, 2014·Nature·Mark A CzuczmanJohn H Brumell
Oct 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·John R ChevilletMuneesh Tewari
Nov 15, 2014·Journal of Extracellular Vesicles·Dennis K JeppesenMarie S Ostenfeld
Dec 10, 2014·EMBO Reports·Jeffrey S SchoreyVictoria L Smith
Feb 20, 2016·Nature Communications·Christian K HolmSøren R Paludan
Sep 28, 2016·Trends in Biochemical Sciences·Liliane ChristHarald Stenmark
May 10, 2017·The Journal of Experimental Medicine·Silvia CerboniNicolas Manel
Jun 16, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bridget LarkinAlexander Poltorak
Aug 8, 2017·The Journal of Clinical Investigation·Benson OgunjimiTrine H Mogensen
Sep 7, 2017·Nature Communications·Muhammet F GulenAndrea Ablasser

❮ Previous
Next ❯

Citations

Oct 9, 2019·Current Opinion in Organ Transplantation·Zhizhao ChenAdrian E Morelli
Dec 11, 2019·Nature Immunology·Andrea Ablasser, Sun Hur
Jul 14, 2020·Immunological Reviews·Timur LiwinskiEran Elinav
Feb 8, 2020·Science·Raghu Kalluri, Valerie S LeBleu
May 20, 2020·Nature Reviews. Molecular Cell Biology·Karl-Peter Hopfner, Veit Hornung
Oct 8, 2020·International Journal of Molecular Sciences·Miriam MojzeszJun-Ichi Hikima
Nov 11, 2020·Molecular Cell·Lauren J LaheyLingyin Li
Jan 18, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Lina Herhaus
Dec 19, 2020·Frontiers in Immunology·Jean-Marie BerthelotJean Sibilia
Dec 18, 2020·Frontiers in Immunology·Weinian LiaoJunping Wang
Mar 2, 2021·Biochemical Pharmacology·Ya-Nan PiGe Lou
Mar 16, 2021·Open Biology·Melania BalzaroloMonika C Wolkers
Mar 27, 2021·Cellular & Molecular Immunology·Qiuya YuShufang Cui
Jun 4, 2021·Journal of Cell Science·Jeffrey S SchoreyWilliam R McManus
May 23, 2021·Advanced Drug Delivery Reviews·Anna Lena JungBirke J Benedikter
Oct 16, 2020·Experimental Parasitology·Alejandro Acosta-DávilaJorge Enrique Gómez-Marín

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
confocal microscopy
AFM
electrophoresis
atomic force microscopy
transfections
flow cytometry
enzyme-linked immunosorbent assay
Fluorescence
nuclear translocation

Software Mentioned

MaxQuant
IDEAS
CLC bio Workbench
iT
Andromeda
Xcalibur
NTA
ImageJ
FlowJo
Click

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

© 2022 Meta ULC. All rights reserved