The innate immune response to allotransplants: mechanisms and therapeutic potentials

Feb 27, 2019Cellular & molecular immunology

How the body's natural immune defense reacts to transplanted organs and possible treatments

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Surgical trauma and ischemia reperfusion injury (IRI) trigger a complex inflammatory process that impacts organ transplant outcomes.

Donor organ procurement and engraftment lead to innate immune activation and cell death.
Dying cells release damage-associated molecular patterns (DAMPs) that activate recipient innate immune cells.
Activation involves the complement cascade and toll-like receptors (TLRs), which alert macrophages and dendritic cells.
Innate immune cell inflammation may result in changes to cellular metabolism, promoting aerobic glycolysis.
Proinflammatory cytokines play a role in both innate immune activation and T-cell expansion during allograft rejection.
Early events in innate immunity after transplantation could influence the adaptive immune response and allograft survival.

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Surgical trauma and ischemia reperfusion injury (IRI) are unavoidable aspects of any solid organ transplant procedure. They trigger a multifactorial antigen-independent inflammatory process that profoundly affects both the early and long-term outcomes of the transplanted organ. The injury associated with donor organ procurement, storage, and engraftment triggers innate immune activation that inevitably results in cell death, which may occur in many different forms. Dying cells in donor grafts release damage-associated molecular patterns (DAMPs), which alert recipient innate cells, including macrophages and dendritic cells (DCs), through the activation of the complement cascade and toll-like receptors (TLRs). The long-term effect of inflammation on innate immune cells is associated with changes in cellular metabolism that skew the cells towards aerobic glycolysis, resulting in innate immune cell activation and inflammatory cytokine production. The different roles of proinflammatory cytokines in innate immune activation have been described, and these cytokines also stimulate optimal T-cell expansion during allograft rejection. Therefore, early innate immune events after organ transplantation determine the fate of the adaptive immune response. In this review, we summarize the contributions of innate immunity to allograft rejection and discuss recent studies and emerging concepts in the targeted delivery of therapeutics to modulate the innate immune system to enhance allograft survival.

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The innate immune response to allotransplants: mechanisms and therapeutic potentials

Abstract

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