Innate immunity in lung transplantation

Abstract

Innate immune pathways early after pulmonary transplantation have been shown to cause primary graft dysfunction (PGD) and also predispose to late graft failure. Recent studies in animal models have elucidated critical mechanisms governing such innate immune responses. Here, we discuss pathways of inflammatory cell death, triggers for sterile and infectious inflammation, and signaling cascades that mediate lung injury early after transplantation. These studies highlight potential avenues for lung-specific therapies early following lung transplantation to dampen innate immune responses and improve outcomes.

Keywords: cell death; damage-associated molecular patterns; graft rejection; innate immunity; lung transplantation.

Figure 1

Activation of innate immune responses following lung transplantation. Inflammatory cell death leads to the release of endogenous ligands that propagate inflammatory responses through activation of innate immune signaling pathways. Illustration credit: Erin Neill. ATP, Adenosine triphosphate; DAMP, Damage-associated molecular pattern; HMGB1, High-mobility group box 1; LMW-HA, Low-molecular-weight hyaluronic acid; LPS Lipopolysaccharide; MPTP, Mitochondrial permeability transition pore; mtDNA, Mitochondrial DNA; MyD88, Myeloid differentiation factor 88; NF-κB, Nuclear factor kappa-light-chain enhancer of activated B cells; PAMP, Pathogen-associated molecular pattern; RAGE, Receptor for advanced glycation end products; TLR, Toll-like receptor; TRIF, Toll/Interleukin-1 receptor domain-containing adaptor-inducing interferon-beta.