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

MP Wandel, BH Kim, ES Park, KB Boyle, K Nayak… - Nature …, 2020 - nature.com
MP Wandel, BH Kim, ES Park, KB Boyle, K Nayak, B Lagrange, A Herod, T Henry
Nature immunology, 2020nature.com
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 …
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.
nature.com
以上显示的是最相近的搜索结果。 查看全部搜索结果