Journal
CELL REPORTS
Volume 31, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.03.030
Keywords
-
Categories
Funding
- NIH [R21 AI44139, R01 AI44139, R01 AI063428, K08 AI102945, T32 HL007627, K08 AR075850, R01 HL124209]
- American Asthma Foundation
- Alex's Lemonade Stand Foundation for Childhood Cancer
- V Foundation for Cancer Research
Ask authors/readers for more resources
Interleukin-1 beta (IL-1 beta) is a key orchestrator of anti-microbial immunity whose secretion is typically dependent on activation of inflammasomes. However, many pathogens have evolved strategies to evade inflammasome activation. Here we describe an alternative, two-cell model for IL-1 beta release where invariant natural killer T (iNKT) cells use the death receptor pathway to instruct antigen-presenting cells to secrete IL-1 beta. Following cognate interactions with TLR-primed bone marrow-derived dendritic cells (BMDCs), iNKT cells rapidly translocate intracellular Fas ligand to the surface to engage Fas on BMDCs. Fas ligation activates a caspase-8-dependent signaling cascade in BMDCs that drives IL-1 beta release largely independent of inflammasomes. The apoptotic program initiated by Fas ligation rapidly transitions into a pyroptosis-like form of cell death mediated by gasdermin D. Together, our findings support a two-cell model for IL-1 beta secretion that may supersede inflammasome activation when cytosolic triggers fail.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available