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

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Intracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling. / Nandakumar, Ramya; Tschismarov, Roland; Meissner, Felix; Prabakaran, Thaneas; Krissanaprasit, Abhichart; Farahani, Ensieh; Zhang, Bao cun; Assil, Sonia; Martin, Amandine; Bertrams, Wilhelm; Holm, Christian K.; Ablasser, Andrea; Klause, Tanja; Thomsen, Martin K.; Schmeck, Bernd; Howard, Kenneth A.; Henry, Thomas; Gothelf, Kurt V.; Decker, Thomas; Paludan, Søren R.

In: Nature Microbiology, Vol. 4, 04.2019, p. 701-713.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Nandakumar, R, Tschismarov, R, Meissner, F, Prabakaran, T, Krissanaprasit, A, Farahani, E, Zhang, BC, Assil, S, Martin, A, Bertrams, W, Holm, CK, Ablasser, A, Klause, T, Thomsen, MK, Schmeck, B, Howard, KA, Henry, T, Gothelf, KV, Decker, T & Paludan, SR 2019, 'Intracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling', Nature Microbiology, vol. 4, pp. 701-713. https://doi.org/10.1038/s41564-019-0367-z

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Author

Nandakumar, Ramya ; Tschismarov, Roland ; Meissner, Felix ; Prabakaran, Thaneas ; Krissanaprasit, Abhichart ; Farahani, Ensieh ; Zhang, Bao cun ; Assil, Sonia ; Martin, Amandine ; Bertrams, Wilhelm ; Holm, Christian K. ; Ablasser, Andrea ; Klause, Tanja ; Thomsen, Martin K. ; Schmeck, Bernd ; Howard, Kenneth A. ; Henry, Thomas ; Gothelf, Kurt V. ; Decker, Thomas ; Paludan, Søren R. / Intracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling. In: Nature Microbiology. 2019 ; Vol. 4. pp. 701-713.

Bibtex

@article{5566458bad48483d883e537836c4d126,
title = "Intracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling",
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.",
keywords = "CELLS, DNA, INFECTION, INNATE IMMUNITY, INTERCELLULAR TRANSFER, LISTERIA-MONOCYTOGENES, MICE LACKING, RESPONSES, RNA, SENSOR",
author = "Ramya Nandakumar and Roland Tschismarov and Felix Meissner and Thaneas Prabakaran and Abhichart Krissanaprasit and Ensieh Farahani and Zhang, {Bao cun} and Sonia Assil and Amandine Martin and Wilhelm Bertrams and Holm, {Christian K.} and Andrea Ablasser and Tanja Klause and Thomsen, {Martin K.} and Bernd Schmeck and Howard, {Kenneth A.} and Thomas Henry and Gothelf, {Kurt V.} and Thomas Decker and Paludan, {S{\o}ren R.}",
year = "2019",
month = apr,
doi = "10.1038/s41564-019-0367-z",
language = "English",
volume = "4",
pages = "701--713",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Intracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling

AU - Nandakumar, Ramya

AU - Tschismarov, Roland

AU - Meissner, Felix

AU - Prabakaran, Thaneas

AU - Krissanaprasit, Abhichart

AU - Farahani, Ensieh

AU - Zhang, Bao cun

AU - Assil, Sonia

AU - Martin, Amandine

AU - Bertrams, Wilhelm

AU - Holm, Christian K.

AU - Ablasser, Andrea

AU - Klause, Tanja

AU - Thomsen, Martin K.

AU - Schmeck, Bernd

AU - Howard, Kenneth A.

AU - Henry, Thomas

AU - Gothelf, Kurt V.

AU - Decker, Thomas

AU - Paludan, Søren R.

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

KW - CELLS

KW - DNA

KW - INFECTION

KW - INNATE IMMUNITY

KW - INTERCELLULAR TRANSFER

KW - LISTERIA-MONOCYTOGENES

KW - MICE LACKING

KW - RESPONSES

KW - RNA

KW - SENSOR

UR - http://www.scopus.com/inward/record.url?scp=85062064558&partnerID=8YFLogxK

U2 - 10.1038/s41564-019-0367-z

DO - 10.1038/s41564-019-0367-z

M3 - Journal article

C2 - 30804548

AN - SCOPUS:85062064558

VL - 4

SP - 701

EP - 713

JO - Nature Microbiology

JF - Nature Microbiology

SN - 2058-5276

ER -