Michigan大學(xué)的科學(xué)家最新研究發(fā)現(xiàn),，免疫細(xì)胞并不是等待細(xì)菌結(jié)合到其表面受體之后才被觸發(fā)，細(xì)菌可以進(jìn)入這些細(xì)胞內(nèi)部,，然后各自觸發(fā)強(qiáng)大的免疫反應(yīng),，這和之前科學(xué)家們想象的很不一樣。
這一結(jié)果發(fā)表在4月的《免疫學(xué)》（Immunity）上,，它描述了身體是怎樣識別入侵的細(xì)菌并做出反應(yīng)的很多細(xì)節(jié),。UM的這一結(jié)果提供了更好設(shè)計未來人類疫苗的想法，同時也帶來了更精確治療例如風(fēng)濕性關(guān)節(jié)炎等自體免疫疾病的方法,。
UM醫(yī)學(xué)院病理學(xué)教授Gabriel Núñez說：“我們的研究證明細(xì)菌在細(xì)胞內(nèi)引發(fā)免疫反應(yīng),。”多年以來，科學(xué)家一直相信,，當(dāng)細(xì)菌入侵人體時,，它們和免疫細(xì)胞表面受體接合觸發(fā)免疫反應(yīng)。但是Nunez小組發(fā)現(xiàn)了新路徑,。
當(dāng)細(xì)菌進(jìn)入免疫細(xì)胞時,，一種叫做cryopyrin的蛋白被激活。在去年的《自然》（Nature）上，Nunez小組曾報道過cryopyrin在多種炎癥反應(yīng)中都參與其中,。cryopyrin將激活一種關(guān)鍵的觸發(fā)炎癥反應(yīng)的酶——capsace-1,，這種酶會產(chǎn)生IL-1beta——一種強(qiáng)大的傳遞給免疫系統(tǒng)對抗病原體信號的分子，并產(chǎn)生發(fā)熱以對抗細(xì)菌,。
在新文章中,，科學(xué)家描述了cryopyrin是如何激活這一過程的。結(jié)果表明,，cryopyrin不需要通過著名的細(xì)胞表面受體TLR,。相反的，細(xì)菌通過細(xì)胞膜上的小孔進(jìn)入細(xì)胞,，然后觸發(fā)免疫反應(yīng),，科學(xué)家發(fā)現(xiàn)一種叫做pannexin-1的蛋白產(chǎn)生了這些小孔。UM的科學(xué)家們認(rèn)為,，對于這些過程的認(rèn)識能幫助我們更好的了解人類免疫系統(tǒng)的工作機(jī)制,。
原始出處：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
[email protected]
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.
