炎症体
上睑下垂
细胞生物学
生物
信号转导
目标2
TLR4型
先天免疫系统
特里夫
半胱氨酸蛋白酶1
炎症
分泌物
免疫系统
免疫学
Toll样受体
生物化学
作者
Moritz M. Gaidt,Thomas S. Ebert,Dhruv Chauhan,Tobias Schmidt,Jonathan L. Schmid‐Burgk,Francesca Rapino,Avril A. B. Robertson,Matthew A. Cooper,Thomas Graf,Veit Hornung
出处
期刊:Immunity
[Elsevier]
日期:2016-03-30
卷期号:44 (4): 833-846
被引量:638
标识
DOI:10.1016/j.immuni.2016.01.012
摘要
Summary
Interleukin-1β (IL-1β) is a cytokine whose bioactivity is controlled by activation of the inflammasome. However, in response to lipopolysaccharide, human monocytes secrete IL-1β independently of classical inflammasome stimuli. Here, we report that this constituted a species-specific response that is not observed in the murine system. Indeed, in human monocytes, lipopolysaccharide triggered an "alternative inflammasome" that relied on NLRP3-ASC-caspase-1 signaling, yet was devoid of any classical inflammasome characteristics including pyroptosome formation, pyroptosis induction, and K+ efflux dependency. Genetic dissection of the underlying signaling pathway in a monocyte transdifferentiation system revealed that alternative inflammasome activation was propagated by TLR4-TRIF-RIPK1-FADD-CASP8 signaling upstream of NLRP3. Importantly, involvement of this signaling cascade was limited to alternative inflammasome activation and did not extend to classical NLRP3 activation. Because alternative inflammasome activation embraces both sensitivity and promiscuity of TLR4, we propose a pivotal role for this signaling cascade in TLR4-driven, IL-1β-mediated immune responses and immunopathology in humans.
科研通智能强力驱动
Strongly Powered by AbleSci AI