Figure 7. Model of TRIF-mediated signaling following hepatocyte death.

Following hepatocyte death, there are multiple mechanisms by which inflammation may be propagated in the liver via TRIF signaling pathways. (A) Dying hepatocytes may themselves up-regulate inflammatory transcripts, (B) neighboring, live hepatocytes may up-regulate inflammatory transcripts in response to inflammatory mediators produced by LSECs or KCs or by dying hepatocytes, or (C) DAMPs and other inflammatory mediators released by dying hepatocytes may induce the death of neighboring hepatocytes, propagating the cycle of death and inflammation. (D) The production of myeloid cell recruitment factors by dying hepatocytes, live hepatocytes, and/or other liver cells results in Ly6C^hi monocyte infiltration which may (E) differentiate into Ly6C^lo monocyte-derived macrophages that likely aid in tissue repair. DAMPs; damage-associated molecular patterns; KC, Kupffer cell; LSEC, liver sinusoidal endothelial cell; and TRIF, TIR-domain-containing adapter-inducing interferon-β.