CD14 acts as a co-factor for the Toll-like receptor TLR4 to activate inflammatory responses to lipopolysaccharides. In Immunity, Zanoni et al. report that CD14 recognizes host-derived inflammatory lipids composed of oxidized phosphrylcholine derivatives released from dying cells. Such recognition triggers transient down-regulation of CD14 from the cell surface and cytosolic caspase-11-dependent activation of the inflammasome, independently of TLR4 responses. Exposure to oxidized phosphrylcholine components, specifically 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-(5'-oxo-valeroyl)sn-glycero-3-phosphocholine, leads to hyperactivation of dendritic cells and macrophages and prolonged release of IL-1 without triggering cell death via pyroptosis. Hence, exposure to these sterile damage-associated molecular patterns leads to chronic inflammation in vivo.

Immunity 47, 697–709 (2017)