Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs

Abstract:Fusobacterium nucleatum (F. nucleatum) is the early pathogenic colonizer of periodontitis, while the host response to this pathogen infection remains unclear yet. In this study, we built the F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, facilitates apoptosis, ferroptosis, and inflammatory cytokines production in a dose-dependent manner. F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of IL-1β, IL-6 and IL-8. Further study showed FadA could bind with PEBP1 to active Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process of PDLSCs with the increasing duration of F. nucleatum infection. NFκB1 and NFκB2 were up-regulated since 3 h of F. nucleatum-infection and time serially elevated the inflammatory related genes on the NF-κB signaling pathway. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum-infection.