Human monocytes engage an alternative inflammasome pathway

Gaidt, Moritz M., Ebert, Thomas S., Chauhan, Dhruv, Schmidt, Tobias, Schmid-Burgk, Jonathan L., Rapino, Francesca, Robertson, Avril A. B., Cooper, Matthew A., Graf, Thomas and Hornung, Veit (2016) Human monocytes engage an alternative inflammasome pathway. Immunity, 44 4: 833-846. doi:10.1016/j.immuni.2016.01.012

Author Gaidt, Moritz M.
Ebert, Thomas S.
Chauhan, Dhruv
Schmidt, Tobias
Schmid-Burgk, Jonathan L.
Rapino, Francesca
Robertson, Avril A. B.
Cooper, Matthew A.
Graf, Thomas
Hornung, Veit
Title Human monocytes engage an alternative inflammasome pathway
Journal name Immunity   Check publisher's open access policy
ISSN 1097-4180
Publication date 2016-05-19
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.immuni.2016.01.012
Open Access Status Not Open Access
Volume 44
Issue 4
Start page 833
End page 846
Total pages 14
Place of publication Cambridge, MA United States
Publisher Cell Press
Collection year 2017
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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