Periodontopathogene Bakterien: Freisetzungsmuster von Zytokinen im humanen Vollblut-Testsystem und Unterschiede in der Aktivierung des angeborenen Immunsystems durch Toll-like Rezeptor-Stimulation

Recognition of gram-negative and gram-positive bacteria by innate immune system using “pathogen associated molecular patterns” (PAMP) is mediated by Toll-like receptors (TLRs). Different TLRs share common signalling pathways yet exhibit specificity as well. Periodontal disease is initiated and maintained in the first line by gram-negative but also gram-positive bacterial infection of the gingival sulcus. To date only limited information is available on whether gram-positive and gram-negative bacteria induce different host responses (strength or quality). To elucidate these differential effects this work focused on proinflammatory cytokine releases by assessing ex vivo stimulation of whole blood with heat-killed gram-negative and gram-positive bacteria and thereof derived microbial products associated with distinct TLRs. Tumor necrosis factor-α and interleukin-8 release were measured in the supernatants by enzyme-linked immunosorbent assay. In addition, TLR-transfected HEK-293 cells were stimulated and innate immune responses of peritoneal macrophages from mice lacking TLR2 and TLR4 were tested. The results showed gram-negative and gram-positive species, involved in parodontal disease, inducing distinct patterns of cytokine production. Gram-negative species produced higher amounts of tumor necrosis factor-α while gram-positive species released higher amounts of the chemokine interleukin-8. Data from TLR knockout mice and TLR-transfected HEK-293 cells revealed a somehow specific role of TLR4 and TLR2 for the recognition of gram-negative and gram-positive bacteria. Interestingly F. nucleatum and P. gingivalis differed from the observations made for other gram-negative Bacteria. The revealed data demonstrate that periodontopathogenic gram-negative and gram-positive bacterial species induced different patterns of immunoregulatory activity, which is interpreted as the result of variable activation of different TLRs. These findings were discussed against the backround of parodontal disease and mucosal immunity.