Prevotella intermedia-Derived Extracellular Vesicles Promote Pulpitis

Although bacterial infection is the primary etiological factor of pulpitis, the underlying mechanisms remain unclear. Bacterial extracellular vesicles (BEVs) play significant roles in the pathogenesis of infectious diseases independent of bacteria. However, the involvement of BEVs in pulpitis has yet to be explored. In this study, we investigated for the first time the specific mechanisms of action of EVs derived from Prevotella intermedia (Pi) in pulpitis. Our results revealed that Pi-EVs were taken up by macrophages, which amplified their pathogenic effects, thereby inducing inflammation in dental pulp cells (DPCs) and contributing to the progression of pulpitis. Mechanistically, Pi-EVs caused macrophage necroptosis to promote interleukin-33 (IL-33) secretion. Secreted IL-33 subsequently targeted DPCs, inducing endoplasmic reticulum (ER) stress and driving the development of pulpitis. Taken together, our study identified Pi-EVs as a potential virulence factor in pulpitis and revealed a previously unrecognized pathogenic cascade: Pi-EVs - macrophage necroptosis - IL-33 - ER stress in DPCs. To our knowledge, this is the first investigation of pulpitis development from the perspective of bacterial extracellular vesicles. Our study expands the understanding of pulpitis pathogenesis by highlighting the role of bacterial-host cell interactions and may offer new targeted therapeutic strategies for pulpitis.