Toll-like receptor 2 and renal allograft function.
BACKGROUND
Toll-like receptors (TLR) modulate the immune response. We analyzed the relationships between TLR expression in renal tissue with infection, rejection and graft function after kidney transplantation.


METHODS
TLR-2 and TLR-4 expression was detected by immunohistochemistry in 257 protocol biopsies obtained 6 weeks, 3 and 6 months after transplantation, and in 108 indication biopsies. We correlated TLR expression in different renal tissue compartments with kidney transplant function 6, 12 and 24 months after transplantation, acute cellular rejection in renal grafts (according to the Banff classification), and urinary tract and cytomegalovirus infections.


RESULTS
We found a highly consistent correlation of TLR-2 expression in proximal and distal tubules, and in renal vessels (p < 0.001 for all compartments), but not for TLR-4 expression. This holds true for all protocol biopsy time points as well as for indication biopsies. Positive TLR-2 expression in renal tubules was associated with significantly (p < 0.05) better initial graft function as well as graft function 6, 12 and 24 months after transplantation. We also found a significant (p < 0.05) association between TLR-2 expression and lower incidence of acute cellular rejection in early protocol biopsies (6 weeks). In contrast, positive TLR-4 expression was not related to kidney function or acute cellular rejection. Further, the two different TLR subtypes were not related to episodes of urinary tract or cytomegalovirus infections.


CONCLUSIONS
TLR-2 expression in renal tissue is associated with superior graft function up to 2 years after kidney transplantation. The role of TLR-2 in the immune response against human kidney transplants warrants further investigation.
de Groot
Kirsten
K
Department of Internal Medicine, Hannover Medical School, Hannover, Germany.
Kuklik
Katharina
K
Bröcker
Verena
V
Schwarz
Anke
A
Gwinner
Wilfried
W
Kreipe
Hans
H
Haller
Hermann
H
Fliser
Danilo
D
Mengel
Michael
M
D001706:Biopsy; D003586:Cytomegalovirus Infections / Q000378:metabolism; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007668:Kidney / Q000737:chemistry; D016030:Kidney Transplantation; D007686:Kidney Tubules, Distal / Q000737:chemistry; D007687:Kidney Tubules, Proximal / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000032:analysis* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000502:physiology; D014184:Transplantation, Homologous; D014552:Urinary Tract Infections / Q000378:metabolism
D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4