英国剑桥大学Felix Randow、Michal P. Wandel等研究人员合作发现,鸟苷酸结合蛋白能够将胞浆细菌转化为半胱氨酸蛋白酶-4信号平台。该项研究成果于2020年6月15日在线发表在《自然—免疫学》杂志上。
Title: Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms
Author: Michal P. Wandel, Bae-Hoon Kim, Eui-Soon Park, Keith B. Boyle, Komal Nayak, Brice Lagrange, Adrian Herod, Thomas Henry, Matthias Zilbauer, John Rohde, John D. MacMicking, Felix Randow
Issue&Volume: 2020-06-15
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.
DOI: 10.1038/s41590-020-0697-2
Source: https://www.nature.com/articles/s41590-020-0697-2
Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex