Role of innate immunity in primary graft dysfunction after lung transplantation

Abstract

Primary graft dysfunction (PGD), a form of acute lung injury after lung transplantation, has a significant impact on clinical outcomes after lung transplantation. This potentially reversible graft impairment occurs after ischemia-reperfusion injury. This review describes the expanding body of literature evaluating the central role of innate immune activation, nonadaptive responses and dysregulation in the development of PGD after lung transplant. The innate immune system, highlighted by Toll-like receptor pathways and neutrophil migration and influx, plays an important role in the initiation and propagation of ischemia-reperfusion injury. Recent plasma biomarker and gene association studies have identified several genes and proteins composing innate immune pathways to be associated with PGDs. Long pentraxin-3 and Toll-like receptors, as well as inflammasomes and Toll-interacting protein, are associated with the development of PGD after lung transplantation. Innate immune pathways are involved in the development of PGD and may provide attractive targets for therapies. It may be possible to prevent or treat PGD, as well as to allow pre-transplant PGD risk stratification. To improve understanding of the mechanisms behind clinical risk factors for PGD will require further in-depth correlation of donor-specific and recipient-related triggers of nonadaptive immune responses.