Toll-like-Rezeptor Expression humaner dendritischer Zellen - Differentielle Expression von Toll-Like-Rezeptoren durch humane myeloide dendritische Zellen und Einfluss der Expression auf die Funktion beispielhaft an den TLR2, 3, 4 und 9

In this study the expression of Toll-Like-Resceptors during the progression of monocytes to dendritic cells (DC) of different stages of maturarition was examined. CD14+ monocytes of peripheral human blood where cultured with Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) and thus matured to immature dendritic cells (iDC). These cells were then characterized by their expression of surface molecules, their phagocytosis capability and their capacity to activate in the mixed leucocyte reaction (MLR). The expression of TLR2, 3, 4 and 9 was determined by real-time PCR, their function was tested by highly specific ligands for the particular receptor (TLR2: LTA, TLR4: LPS, TLR9: synthetic CPG-oligonucleotides). Expression and function of TLR 2 and TLR4 on myeloid DC could be demonstrated throughout all stages of development. TLR 9 could not be detected and a specific stimulation of cells by CpG-ODN was not possible. Expression of TLR3 was shown after stimulation of iDC with GM-CSF or LPS. The findings showed that myeloid DC have been generated, proved by their expression of surface molecules and their complex functions. These DC exposed TLR2 and TLR4 during all stages of maturation, but never TLR9. A reaction to ODN was therefore never seen. On one hand the lack of TLR9 explains the missing reaction to ODN-stimulation, on the other hand the necessity of TLR9 for ODN-recognition could be emphasized. The expression of the fourth analyzed TLR, TLR3, still raises questions: the necessity of a receptor for viral dsRNA on mature human myeloid DC, and thence the question for the function of human TLR3. How TLR3-signaling functions, how much it differs from other TLR-signaling, remains as elusive as the differences of the human and the murine immune system concerning the expression of TLR3. In this study a significant discrepancy between mice and men – al least in TLR-expression on DC – could be shown. A comparison of adult versus naive human DC was touched on without further deepening. An immersion would have exceeded this dissertation partly due to a lack of literature. Out of the findings again a differing expression of TLR3 remains interesting – DC cultured out of naive cells do not express TLR3. At large the lack of literature concerning a comparison of the naive versus the adult human immune system is astonishing. Future prospects are taking a closer look on TLR3 function and signaling as well as comparing naive versus adult human immune system, particularly with regard to dendritic cells – the “distributing centre” of the immune response. A better comprehension of the differences of human and murine immune system might be brought up by these findings.