| First Author | Donado CA | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 1 | Pages | 107466 |
| PubMed ID | 32268091 | Mgi Jnum | J:310108 |
| Mgi Id | MGI:6715279 | Doi | 10.1016/j.celrep.2020.03.030 |
| Citation | Donado CA, et al. (2020) A Two-Cell Model for IL-1beta Release Mediated by Death-Receptor Signaling. Cell Rep 31(1):107466 |
| abstractText | Interleukin-1beta (IL-1beta) 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-1beta release where invariant natural killer T (iNKT) cells use the death receptor pathway to instruct antigen-presenting cells to secrete IL-1beta. 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-1beta 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-1beta secretion that may supersede inflammasome activation when cytosolic triggers fail. |
