Details

Autor(en) / Beteiligte

• Watson, Robert O.
• Bell, Samantha L.
• MacDuff, Donna A.
• Kimmey, Jacqueline M.
• Diner, Elie J.
• Olivas, Joanna
• Vance, Russell E.
• Stallings, Christina L.
• Virgin, Herbert W.
• Cox, Jeffery S.

Titel

The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy

Ist Teil von

• Cell host & microbe, 2015-06, Vol.17 (6), p.811-819

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Type I interferons (IFNs) are critical mediators of antiviral defense, but their elicitation by bacterial pathogens can be detrimental to hosts. Many intracellular bacterial pathogens, including Mycobacterium tuberculosis, induce type I IFNs following phagosomal membrane perturbations. Cytosolic M. tuberculosis DNA has been implicated as a trigger for IFN production, but the mechanisms remain obscure. We report that the cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), is required for activating IFN production via the STING/TBK1/IRF3 pathway during M. tuberculosis and L. pneumophila infection of macrophages, whereas L. monocytogenes short-circuits this pathway by producing the STING agonist, c-di-AMP. Upon sensing cytosolic DNA, cGAS also activates cell-intrinsic antibacterial defenses, promoting autophagic targeting of M. tuberculosis. Importantly, we show that cGAS binds M. tuberculosis DNA during infection, providing direct evidence that this unique host-pathogen interaction occurs in vivo. These data uncover a mechanism by which IFN is likely elicited during active human infections. [Display omitted] •cGAS is essential for type I IFN production during M. tuberculosis infection•cGAS activation targets M. tuberculosis to the selective autophagy pathway•cGAS deficiency leads to increased intracellular M. tuberculosis growth•cGAS directly binds to M. tuberculosis genomic DNA during infection During Mycobacterium tuberculosis infection, cytosolic bacterial DNA triggers cell-intrinsic innate immune responses. Watson et al. show that the cytosolic DNA sensor cGAS recognizes M. tuberculosis DNA. This sensing is required for activating pro-bacterial type I interferon expression as well as targeting M. tuberculosis to the anti-bacterial selective autophagy pathway.