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：
原始出处:
Immunity, Vol , Issue ,
Article
Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptor Signaling
Thirumala-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,
1 Department of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
2 Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
3 Department 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.
