细菌与宿主之间的相互作用在全身性疾病的发生和发展中起着至关重要的作用,包括胃肠道和口腔疾病,由于这些病原体分泌各种毒力因子。GroEL,一种由多种口腔致病菌分泌的强效毒力因子,与牙龈上皮的损伤有关,牙周膜,牙槽骨和其他外周组织。然而,潜在的生物力学在很大程度上仍然未知。在本研究中,我们验证了GroEL可以触发NLRP3炎性体及其下游效应分子的激活,IL-1β和IL-18在人牙周膜干细胞(hPDLSCs)中,并导致明胶酶(MMP-2和MMP-9)的高度激活,以促进细胞外基质(ECM)的降解。GroEL介导的NLRP3炎性体激活需要Toll样受体(TLR2和TLR4)的参与。TLR2和TLR4的高上调诱导NF-κB(p-p65)信号增强并促进其核积累,从而激活NLRP3炎性体。这些结果在直接注射GroEL的大鼠模型中得到证实。总的来说,本研究揭示了毒力因子在细菌诱导宿主免疫应答中的作用,也可能为牙周炎的预防提供新的线索。
The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens.
GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that
GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1β and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM).
GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of
GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.