Toll-like receptor signaling in transplantation.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Alegre
Maria-Luisa
ML
Department of Medicine, The University of Chicago, Chicago, Illinois, USA. malegre@midway.uchicago.edu
Goldstein
Daniel R
DR
Chong
Anita S
AS
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology; D008024:Ligands; D016377:Organ Transplantation / Q000009:adverse effects*; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000187:drug effects / Q000276:immunology*
D007166:Immunosuppressive Agents; D008024:Ligands; D051193:Toll-Like Receptors