Toll-like receptor pathways and innate responses to allografts

PURPOSE OF REVIEW: There is an increasing appreciation of the role of the innate immune system in modulating alloimmunity following organ transplantation. This review will outline the studies that have investigated the role of the Toll-like receptors in allograft rejection. RECENT FINDINGS: Evidence indicates that Toll like receptors are involved in acute allograft rejection by inducing dendritic cells to mature and migrate to the draining lymph nodes and initiate Th1 alloimmune responses. Within the last year the impact of Toll-like receptor activation on transplantation tolerance has been investigated. Two studies have shown that Toll-like receptor activation can prevent the induction of transplantation tolerance whereas our own study has shown that deficiency in Toll-like receptor signaling facilitates transplantation tolerance. Finally, a recent study indicated that fragmented hyaluronan, part of the extracellular matrix, might be one of the endogenous Toll-like receptor activators in the setting of alloimmunty. SUMMARY: Toll-like receptors play an important role in modulating the alloimmune response. Their manipulation may have profound effects on the induction of transplantation tolerance. Future investigation into other aspects of innate immunity and their influence on solid organ transplantation will likely yield important insights to the field.