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Aryl-functionalised α,α′-Trehalose 6,6′-Glycolipid Induces Mincle-independent Pyroptotic Cell Death by Kristel Kodar; Emma M. Dangerfield; Amy J. Foster; Devlin Forsythe; Shigenari Ishizuka; Melanie J. McConnell; Sho Yamasaki; Mattie S. M. Timmer; Bridget L. Stocker is a Immunology and Microbiology article available to read on EtoBox.

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## __Abstract__— α,α′-Trehalose 6,6′-glycolipids have long been known for their immunostimulatory properties. The adjuvanticity of α,α′-trehalose 6,6′-glycolipids is mediated by signalling through the macrophage inducible C-type lectin (Mincle) and the induction of an inflammatory response. Herein, we present an aryl-functionalised trehalose glycolipid, AF-2, that leads to the release of cytokines and chemokines, including IL-6, MIP-2 and TNF-α, in a Mincle-dependent manner. Furthermore, plate-coated AF-2 also leads to the Mincle-independent production of IL-1β, which is unprecedented for this class of glycolipid. Upon investigation into the mode of action of plate-coated AF-2, it was observed that the treatment of WT and Mincle^−/−^ bone marrow derived macrophages (BMDM), murine RAW264.7 cells, and human monocytes with AF-2 led to lytic cell death, as evidenced using Sytox Green and lactate dehydrogenase assays, and confocal and scanning electron microscopy. The requirement for functional Gasdermin D and Caspase-1 for IL-1β production and cell death by AF-2 confirmed pyroptosis as the mode of action of AF-2. The inhibition of NLRP3 and K^+^ efflux reduced AF-2 mediated IL-1β produ

Who reads Aryl-functionalised α,α′-Trehalose 6,6′-Glycolipid Induces Mincle-independent Pyroptotic Cell Death?

Author

Kristel Kodar; Emma M. Dangerfield; Amy J. Foster; Devlin Forsythe; Shigenari Ishizuka; Melanie J. McConnell; Sho Yamasaki; Mattie S. M. Timmer; Bridget L. Stocker

Publisher

Springer Science and Business Media LLC

Published

2023

Language

EN

Field

Immunology and Microbiology (Life Sciences)