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


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Article Info

DATE

2019-04

AUTHORS

Ramya Nandakumar, Roland Tschismarov, Felix Meissner, Thaneas Prabakaran, Abhichart Krissanaprasit, Ensieh Farahani, Bao-cun Zhang, Sonia Assil, Amandine Martin, Wilhelm Bertrams, Christian K. Holm, Andrea Ablasser, Tanja Klause, Martin K. Thomsen, Bernd Schmeck, Kenneth A. Howard, Thomas Henry, Kurt V. Gothelf, Thomas Decker, Søren 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. More... »

PAGES

701-713

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41564-019-0367-z

    DOI

    http://dx.doi.org/10.1038/s41564-019-0367-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112365244

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30804548


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