Michigan大学的科学家最新研究发现，免疫细胞并不是等待细菌结合至其表面受体后才被引发，而是细菌进入这些细胞内部，然后各自引起强大的免疫反应，这和之前科学家们想象不太一样。 研究作者Gabriel Núñez表示，我们的研究证明细菌在细胞内引发免疫反应。当细菌进入免疫细胞时，一种叫做cryopyrin的蛋白被启动。cryopyrin将启动一种关键的触发炎症反应的酶——capsace-1，这种酶会产生IL-1beta，这是一种强大的讯息分子，会传递给免疫系统以对抗病原体。 在这篇新文章中，科学家描述了cryopyrin如何启动这个过程的。研究结果显示，cryopyrin不需要通过著名的细胞表面受体TLR。相反的，细菌通过细胞膜上的小孔进入细胞，然后触发免疫反应，科学家发现一种叫做pannexin-1的蛋白，可以产生了这些小孔。 这项研究结果发表于4月的Immunity上，描述身体如何样识别入侵的细菌并做出反应。这项研究结果提供了更好的想法，有助于设计新的疫苗，同时也能研发出更精确的自体免疫疾病疗法。 (资料来源: Bio.com) 英文原文链接： http://www.bio.com/newsfeatures/newsfeatures_research.jhtml;jsessionid=N2IOBRI2GZPFHR3FQLMSFEWHUWBNQIV0?cid=28200055 原始出处: Immunity, Vol , Issue , Article
Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor SignalingThirumala-Devi Kanneganti,1,4 Mohamed Lamkanfi,1,4 Yun-Gi Kim,1 Grace Chen,2 Jong-Hwan Park,1 Luigi Franchi,1 Peter Vandenabeele,3 and Gabriel Núñez1, 1Department of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
2Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
3Department of Molecular Biomedical Research, Molecular Signalling and Cell Death Unit, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Zwijnaarde, Belgium Corresponding author
Gabriel Núñez
bclx@umich.edu Summary Cryopyrin is essential for caspase-1 activation triggered by Toll-like receptor (TLR) ligands in the presence of adenosine triphosphate (ATP). However, the events linking bacterial products and ATP to cryopyrin remain unclear. Here we demonstrate that cryopyrin-mediated caspase-1 activation proceeds independently of TLR signaling, thus dissociating caspase-1 activation and IL-1β secretion. Instead, caspase-1 activation required pannexin-1, a hemichannel protein that interacts with the P2X7 receptor. Direct cytosolic delivery of multiple bacterial products including lipopolysaccharide, but not flagellin, induced caspase-1 activation via cryopyrin in the absence of pannexin-1 activity or ATP stimulation. However, unlike Ipaf-dependent caspase-1 activation, stimulation of the pannexin-1-cryopyrin pathway by several intracellular bacteria was independent of a functional bacterial type III secretion system. These results provide evidence for cytosolic delivery and sensing of bacterial molecules as a unifying model for caspase-1 activation and position pannexin-1 as a mechanistic link between bacterial stimuli and the cryopyrin inflammasome. 摘自《生物谷》 |
