Michigan大學的科學家最新研究發(fā)現(xiàn)，免疫細胞并不是等待細菌結(jié)合至其表面受體后才被引發(fā),，而是細菌進入這些細胞內(nèi)部,，然后各自引起強大的免疫反應，這和之前科學家們想象不太一樣,。
研究作者Gabriel Núñez表示,，我們的研究證明細菌在細胞內(nèi)引發(fā)免疫反應。當細菌進入免疫細胞時,，一種叫做cryopyrin的蛋白被啟動,。cryopyrin將啟動一種關(guān)鍵的觸發(fā)炎癥反應的酶——capsace-1，這種酶會產(chǎn)生IL-1beta,，這是一種強大的訊息分子,，會傳遞給免疫系統(tǒng)以對抗病原體。
在這篇新文章中,，科學家描述了cryopyrin如何啟動這個過程的,。研究結(jié)果顯示，cryopyrin不需要通過著名的細胞表面受體TLR。相反的,，細菌通過細胞膜上的小孔進入細胞,，然后觸發(fā)免疫反應，科學家發(fā)現(xiàn)一種叫做pannexin-1的蛋白,，可以產(chǎn)生了這些小孔,。
這項研究結(jié)果發(fā)表于4月的Immunity上，描述身體如何樣識別入侵的細菌并做出反應,。這項研究結(jié)果提供了更好的想法,，有助于設計新的疫苗，同時也能研發(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.
