A Two-Cell Model for IL-1? Release Mediated by Death-Receptor Signaling.

ABSTRACT: Interleukin-1? (IL-1?) 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? release where invariant natural killer T (iNKT) cells use the death receptor pathway to instruct antigen-presenting cells to secrete IL-1?. 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? 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? secretion that may supersede inflammasome activation when cytosolic triggers fail.

SUBMITTER: Donado CA 

PROVIDER: S-EPMC7192215 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature