Sensing of cell death by myeloid C-type lectin receptors

Molecules associated with dead or dying cells can be detected by receptors on macrophages and dendritic cells. Signals from these receptors impact myeloid cell function and play a role in determining whether death is silent or proinflammatory, tolerogenic or immunogenic. Prominent among myeloid receptors detecting dead cells are C-type lectin receptors (CLRs). Signals from these receptors variably induce endocytosis of cell corpses, corpse degradation, retrieval of dead cell-associated antigens and/or modulation of immune responses. The sensing of tissue damage by myeloid CLRs complements detection of pathogens in immunity and represents an ancient response aimed at restoring tissue homeostasis.

► Some C-type lectin receptors (CLRs) are involved in uptake of apoptotic cells. ► Other CLRs detect necrotic cells and signal to initiate or modulate inflammation and immunity. ► CLRs can direct dead cell cargo to distinct endocytic compartments. ► DNGR-1 decodes the antigenicity of necrotic cells by regulating cross-presentation of dead cell-associated antigens. ► Mincle sensing of necrotic cells promotes inflammation and neutrophilia.