2025 Volume 3 Issue 1 Pages 2-10
Persistent immunosuppression, or immunoparalysis, in the late stages of sepsis is thought to be a major cause of severe illness. It is thought that endotoxin tolerance occurs in macrophages due to long-term infection with pathogens, causing an inflammatory response. However, the molecular mechanisms involved are largely unknown. We have reported that P. gingivalis, an important causative bacterium of periodontal disease, exhibits a unique cytokine expression pattern compared to E. coli. In this study, in order to elucidate the mechanism of endotoxin tolerance, we used LPS derived from E. coli and P. gingivalis to evaluate whether endotoxin tolerance could be artificially induced, and examined the differences in its effects on immunodeficiency. E. coli LPS primary stimulation significantly suppressed TNFA gene expression in response to E. coli LPS and P. gingivalis LPS secondary stimulation, confirming the induction of endotoxin tolerance. However, when P. gingivalis LPS was used for the primary stimulation, there was no suppression of TNFA expression, indicating that the effects of E. coli LPS and P. gingivalis LPS were different. The endotoxin tolerance induced by the primary stimulation of E. coli LPS was also effective in the secondary stimulation of E. coli and P. gingivalis bacterial antigens. On the other hand, in the case of secondary stimulation with bacterial antigens after primary stimulation with P. gingivalis LPS, the expression of inflammatory cytokines was not suppressed, confirming that P. gingivalis LPS has no endotoxin tolerance-inducing effect. In addition, the expression of the anti-inflammatory cytokine IL10 was significantly enhanced. In studies using B. subtillis PGN as the secondary stimulus, endotoxin tolerance was induced by E. coli LPS primary stimulation, as in the case of P. gingivalis bacterial antigen secondary stimulation, and was not observed, and IL10 expression was enhanced, suggesting the involvement of the TLR-1/TLR-2 signaling pathway in P. gingivalis. P. gingivalis showed interesting results in this endotoxin tolerance induction, in that endotoxin tolerance did not occur, unlike E. coli.
