Toll-like receptor signaling in transplantation

PURPOSE OF REVIEW: This review summarizes recent advances in the role of endogenous and exogenous Toll-like receptor ligands in the activation and inhibition of immune responses in transplantation. RECENT FINDINGS: During an alloresponse, Toll-like receptors can be engaged by both damage-induced endogenous ligands or microbial-associated molecular patterns. The damage-induced molecule high mobility group box 1 protein and its binding to Toll-like receptor 4 have been identified as major initiators of antitumor and antitransplant immune responses. Type I interferon signaling plays an important role in the pro-rejection effect mediated by Toll-like receptor agonists and some bacteria. Similar pathways, however, in neonates can result in inhibition rather than activation of alloimmune responses. SUMMARY: The consequences of Toll-like receptor engagement by endogenous and exogenous ligands in transplantation may depend on the relative induction of inflammatory and regulatory pathways and the stage of development of the immune system.