Unknown

Dataset Information

0

Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms.


ABSTRACT: Bacterial lipopolysaccharide triggers human caspase-4 (murine caspase-11) to cleave gasdermin-D and induce pyroptotic cell death. How lipopolysaccharide sequestered in the membranes of cytosol-invading bacteria activates caspases remains unknown. Here we show that in interferon-γ-stimulated cells guanylate-binding proteins (GBPs) assemble on the surface of Gram-negative bacteria into polyvalent signaling platforms required for activation of caspase-4. Caspase-4 activation is hierarchically controlled by GBPs; GBP1 initiates platform assembly, GBP2 and GBP4 control caspase-4 recruitment, and GBP3 governs caspase-4 activation. In response to cytosol-invading bacteria, activation of caspase-4 through the GBP platform is essential to induce gasdermin-D-dependent pyroptosis and processing of interleukin-18, thereby destroying the replicative niche for intracellular bacteria and alerting neighboring cells, respectively. Caspase-11 and GBPs epistatically protect mice against lethal bacterial challenge. Multiple antagonists of the pathway encoded by Shigella flexneri, a cytosol-adapted bacterium, provide compelling evolutionary evidence for the importance of the GBP-caspase-4 pathway in antibacterial defense.

SUBMITTER: Wandel MP 

PROVIDER: S-EPMC7381384 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms.

Wandel Michal P MP   Kim Bae-Hoon BH   Park Eui-Soon ES   Boyle Keith B KB   Nayak Komal K   Lagrange Brice B   Herod Adrian A   Henry Thomas T   Zilbauer Matthias M   Rohde John J   MacMicking John D JD   Randow Felix F  

Nature immunology 20200615 8


Bacterial lipopolysaccharide triggers human caspase-4 (murine caspase-11) to cleave gasdermin-D and induce pyroptotic cell death. How lipopolysaccharide sequestered in the membranes of cytosol-invading bacteria activates caspases remains unknown. Here we show that in interferon-γ-stimulated cells guanylate-binding proteins (GBPs) assemble on the surface of Gram-negative bacteria into polyvalent signaling platforms required for activation of caspase-4. Caspase-4 activation is hierarchically contr  ...[more]

Similar Datasets

| S-EPMC4000848 | biostudies-literature
| S-EPMC10015372 | biostudies-literature
| S-EPMC7566093 | biostudies-literature
| S-EPMC9589214 | biostudies-literature
| S-SCDT-10_15252-EMBJ_2022112558 | biostudies-other
| S-EPMC3729158 | biostudies-literature
| S-EPMC6060091 | biostudies-literature
| S-EPMC9338265 | biostudies-literature
| S-EPMC8196077 | biostudies-literature
| S-EPMC5571548 | biostudies-literature