Fig. 2.

A schematic view of “trained immunity”. A myeloid cell undergoes a ‘trained’ immune response to a primary stimulus, danger-associated molecule pattern (DAMP) or pathogen-associated molecular pattern (PAMP), which binds and signals through the Toll-like receptor (TLR)2 or TLR4 pathway. This stimulus alters the epigenetic and metabolic state of the cell in a manner that is conserved so as to position it for a hyper-inflammatory response to a secondary stimulus. Secondary stimuli can be immunologically unrelated but, as a result, the elevated expression of pro-inflammatory cytokines to this secondary stimulus can propagate or exacerbate an autoimmune response.