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)合至其表面受體后才被引發(fā)，而是細(xì)菌進(jìn)入這些細(xì)胞內(nèi)部,，然后各自引起強(qiáng)大的免疫反應(yīng),，這和之前科學(xué)家們想象不太一樣。
研究作者Gabriel Núñez表示,，我們的研究證明細(xì)菌在細(xì)胞內(nèi)引發(fā)免疫反應(yīng),。當(dāng)細(xì)菌進(jìn)入免疫細(xì)胞時(shí)，一種叫做cryopyrin的蛋白被啟動(dòng),。cryopyrin將啟動(dòng)一種關(guān)鍵的觸發(fā)炎癥反應(yīng)的酶——capsace-1,，這種酶會(huì)產(chǎn)生IL-1beta，這是一種強(qiáng)大的訊息分子,，會(huì)傳遞給免疫系統(tǒng)以對(duì)抗病原體,。
在這篇新文章中，科學(xué)家描述了cryopyrin如何啟動(dòng)這個(gè)過程的,。研究結(jié)果顯示,，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,，可以產(chǎn)生了這些小孔,。
這項(xiàng)研究結(jié)果發(fā)表于4月的Immunity上，描述身體如何樣識(shí)別入侵的細(xì)菌并做出反應(yīng),。這項(xiàng)研究結(jié)果提供了更好的想法,，有助于設(shè)計(jì)新的疫苗,，同時(shí)也能研發(fā)出更精確的自體免疫疾病療法。
(資料來源 : Bio.com)
英文原文鏈接：
原始出處:
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
[email protected]
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.
