Implication of Toll/IL-1 receptor domain containing adapters in Porphyromonas gingivalis -induced inflammation

Innate immunity

article

Isaac M Bugueno¹  Nadia Benkirane-Jessel¹  Olivier Huck² 

[1] INSERM (French National Institute of Health and Medical Research);Université de Strasbourg;Hôpitaux Universitaires de Strasbourg

关键词: Periodontitis;    inflammation;    infection;    dysbiosis;    TIR;    atherosclerosis;   

DOI  :  10.1177/17534259211013087

来源: Sage Journals

【 摘 要 】

Periodontitis is induced by periodontal dysbiosis characterized by the predominance of anaerobic species. TLRs constitute the classical pathway for cell activation by infection. Interestingly, the Toll/IL-1 receptor homology domain adapters initiate signaling events, leading to the activation of the expression of the genes involved in the host immune response. The aim of this study was to evaluate the effects of Porphyromonas gingivalis on the expression and protein-protein interactions among five TIR adapters (MAL, MyD88, TRIF, TRAM and SARM) in gingival epithelial cells and endothelial cells. It was observed that P. gingivalis is able to modulate the signaling cascades activated through its recognition by TLR4/2 in gingival epithelial cells and endothelial cells. Indeed, MAL-MyD88 protein-protein interactions associated with TLR4 was the main pathway activated by P. gingivalis infection. When transient siRNA inhibition was performed, cell viability, inflammation, and cell death induced by infection decreased and such deleterious effects were almost absent when MAL or TRAM were targeted. This study emphasizes the role of such TIR adapter proteins in P. gingivalis elicited inflammation and the precise evaluation of TIR adapter protein interactions may pave the way for future therapeutics in both periodontitis and systemic disease with a P. gingivalis involvement, such as atherothrombosis.

【 授权许可】

CC BY|CC BY-NC