Role of Toll-Like Receptor–Driven Innate Immunity in Thoracic Organ Transplantation

Polymorphisms in innate immunity genes associated with development of bronchiolitis obliterans after lung transplantation

“…TLR9 was shown to be important in recognizing viral pathogens. 10 One study showed that the homozygous TLR2 Arg753Gln (rs5743708) polymorphism, an SNP not shown to be of risk in our study, is associated with allograft failure after liver transplantation. 18 TLR2 mediates cellular responses to various microbial danger signals including lipoproteins, peptidoglycans from gram-positive bacteria and products from yeast and endogenous ligands.…”

“…10 It is known that genetic polymorphisms of the recipient might correlate with the fate of the transplanted lung. 3,[11][12][13] We hypothesize that polymorphisms in the genes coding for TLRs might contribute to an altered immune response and, finally, to BOS.…”

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

“…These monocytes differentiate into antigen-presenting dendritic cells and recruit and activate T cells, leading to acute alloimmune activation. 16 Because HIFs have a major role in inflammatory responses during ischemia, we hypothesized that HIF-1 in the allograft infiltrating neutrophils and macrophages may play a major role in innate immune responses and the ensuing alloimmune activation. To test this, we used the heterotopic mouse tracheal allograft model and fully major histocompatibility complex (MHC)-mismatched recipients with myeloid-targeted gene deletion of HIF-1α or VHL that leads to constant HIF-1 inactivation or activation, respectively.…”

Extracellular Hmgb1 Functions as an Innate Immune-Mediator Implicated in Murine Cardiac Allograft Acute Rejection

“…However, the contribution of innate immunity to allograft rejection has generally been ignored until the discovery of the Toll-like receptor (TLR) system and the subsequent realization of innate immunity in driving and shaping adaptive immunity (2-4). Thus far, there is compelling evidence that in addition to responding to pathogen-associated molecular patterns (PAMPs) of microorganisms, TLRs also react to endogenous ligands such as heat shock proteins (HSPs), b-defensin, fibronectin, hyaluronan fragments and heparan sulfate (collectively known as damage-associated molecular patterns or DAMPs) (5)(6)(7)(8)(9). Particularly, a number of recent studies revealed that DAMPs not only participate in ischemia/reperfusion related early organ injury, but also play a pivotal role in perpetuating adaptive allograft rejection by signaling through TLRs or other innate receptors such as dectin-1 (10-13).…”