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到其表面受体之后才被触发，细菌可以进入这些细胞内部，然后各自触发强大的免疫反应，这和之前科学家们想象的很不一样。
这一结果发表在4月的《免疫学》（Immunity）上，它描述了身体是怎样识别入侵的细菌并做出反应的很多细节。UM的这一结果提供了更好设计未来人类疫苗的想法，同时也带来了更精确治疗例如风湿性关节炎等自体免疫疾病的方法。
UM医学院病理学教授Gabriel Núñez说：“我们的研究证明细菌在细胞内引发免疫反应。”多年以来，科学家一直相信，当细菌入侵人体时，它们和免疫细胞表面受体接合触发免疫反应。但是Nunez小组发现了新路径。
当细菌进入免疫细胞时，一种叫做cryopyrin的蛋白被激活。在去年的《自然》（Nature）上，Nunez小组曾报道过cryopyrin在多种炎症反应中都参与其中。cryopyrin将激活一种关键的触发炎症反应的酶——capsace-1，这种酶会产生IL-1beta——一种强大的传递给免疫系统对抗病原体信号的分子，并产生发热以对抗细菌。
在新文章中，科学家描述了cryopyrin是如何激活这一过程的。结果表明，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的蛋白产生了这些小孔。UM的科学家们认为，对于这些过程的认识能帮助我们更好的了解人类免疫系统的工作机制。
原始出处：http://www.physorg.com/news95689106.html
部分英文原文：
Immunity，Published April 12, 2007
10.1016/j.immuni.2007.03.008
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
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.
