Universität zu Köln

Wassermann, Ruth, Gulen, Muhammet F., Sala, Claudia ORCID: 0000-0003-4031-4648, Perin, Sonia Garcia, Lou, Ye, Rybniker, Jan, Schmid-Burgk, Jonathan L., Schmidt, Tobias ORCID: 0000-0003-3102-3515, Hornung, Veit ORCID: 0000-0002-4150-194X, Cole, Stewart T. and Ablasser, Andrea (2015). Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1. Cell Host Microbe, 17 (6). S. 799 - 811. CAMBRIDGE: CELL PRESS. ISSN 1934-6069

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Abstract

Cytosolic detection of microbial products is essential for the initiation of an innate immune response against intracellular pathogens such as Mycobacterium tuberculosis (Mtb). During Mtb infection of macrophages, activation of cytosolic surveillance pathways is dependent on the mycobacterial ESX-1 secretion system and leads to type I interferon (IFN) and interleukin-1 beta (IL-1 beta) production. Whereas the inflammasome regulates IL-1 beta secretion, the receptor(s) responsible for the activation of type I IFNs has remained elusive. We demonstrate that the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) is essential for initiating an IFN response to Mtb infection. cGAS associates with Mtb DNA in the cytosol to stimulate cyclic GAMP (cGAMP) synthesis. Notably, activation of cGAS-dependent cytosolic host responses can be uncoupled from inflammasome activation by modulating the secretion of ESX-1 substrates. Our findings identify cGAS as an innate sensor of Mtb and provide insight into how ESX-1 controls the activation of specific intracellular recognition pathways.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wassermann, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Gulen, Muhammet F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sala, Claudia UNSPECIFIED orcid.org/0000-0003-4031-4648 UNSPECIFIED Perin, Sonia Garcia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lou, Ye UNSPECIFIED UNSPECIFIED UNSPECIFIED Rybniker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid-Burgk, Jonathan L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Tobias UNSPECIFIED orcid.org/0000-0003-3102-3515 UNSPECIFIED Hornung, Veit UNSPECIFIED orcid.org/0000-0002-4150-194X UNSPECIFIED Cole, Stewart T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ablasser, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-401175
DOI:	10.1016/j.chom.2015.05.003
Journal or Publication Title:	Cell Host Microbe
Volume:	17
Number:	6
Page Range:	S. 799 - 811
Date:	2015
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1934-6069
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GMP-AMP SYNTHASE; DNA SENSOR; INFECTED MACROPHAGES; ESAT-6 SECRETION; VIRULENCE; INNATE; PATHWAY; CONTRIBUTES; INTERFERONS; RECOGNITION Multiple languages Microbiology; Parasitology; Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40117