Casp11 缺乏会改变龈下微生物群并减轻牙周炎。

Journal of dental research Pub Date : 2024-03-01 Epub Date: 2024-01-10 DOI:10.1177/00220345231221712
S L Fu, Y Y Qian, A N Dai, H Y Li, X H Jin, W T He, S Kang, P H Ding
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引用次数: 0

摘要

牙周炎(PD)是成年人牙齿脱落的主要原因。牙龈卟啉单胞菌(P.g)是一种关键的病原体,已被确定为这一过程的关键因素。人们已认识到牙周病中的裂解酶活化,不断积累的证据强调了 Caspase-11(在人类中被描述为 Caspase-4/5)介导的非典型裂解酶的关键作用。然而,其对帕金森病的影响机制仍不清楚。在本研究中,我们深入研究了 Caspase-11 介导的非典型性热脓毒症、龈下微生物群改变和巨噬细胞极化之间的相互作用。PD患者的临床样本显示,Caspase-4、gasdermin-D及其活性片段的表达增高,这表明非典型脓毒症被激活。单细胞测序分析将Caspase-4与牙龈巨噬细胞联系在一起,强调了它们在白血病中的参与。体外细胞实验证实,P.g诱导的热噬在巨噬细胞中被激活,而Casp11的缺乏会减弱这些效应。在实验性骨髓增生性疾病小鼠模型中,缺乏 Casp11 会导致龈下微生物群组成的改变,并减少牙槽骨的吸收。Casp11-/-小鼠与野生型小鼠同群饲养证实了龈下微生物群的改变,并加剧了牙槽骨的吸收。值得注意的是,Casp11缺陷导致M1极化巨噬细胞减少,与牙槽骨吸收减少相对应,揭示了龈下微生物群改变、巨噬细胞M1极化和牙槽骨吸收之间的联系。总之,我们的研究表明,Caspase-11在肺结核非典型性热蛋白沉积中起着关键作用,可能影响龈下微生物群,并与M1极化有关,而M1极化与牙槽骨吸收有关。这些发现强调了Caspase-11介导的非典型热脓毒症在脓疱病发病机制中的关键作用,并可能为缓解脓疱病的潜在治疗途径提供重要见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Casp11 Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis.

Periodontitis (PD) is the primary cause of tooth loss in adults. Porphyromonas gingivalis (P.g), a keystone pathogen, has been identified as a crucial contributor to this process. Pyroptosis activation in PD is acknowledged, with accumulating evidence underscoring the crucial role of Caspase-11 (described as Caspase-4/5 in humans)-mediated noncanonical pyroptosis. However, the mechanism behind its impact on PD remains unclear. In this study, we delved into the interplay between the Caspase-11-mediated noncanonical pyroptosis, subgingival microbiota alteration, and macrophage polarization. Clinical samples from PD patients revealed heightened expression of Caspase-4, gasdermin-D, and their active fragments, pointing to the activation of the noncanonical pyroptosis. Single-cell sequencing analysis linked Caspase-4 with gingival macrophages, emphasizing their involvement in PD. In vitro cell experiments confirmed that P.g-induced pyroptosis was activated in macrophages, with Casp11 deficiency attenuating these effects. In an experimental PD mouse model, Casp11 deficiency led to an alteration in subgingival microbiota composition and reduced alveolar bone resorption. Casp11-/- mice cohousing with wild-type mice confirmed the alteration of the subgingival microbiota and aggravated the alveolar bone resorption. Notably, Casp11 deficiency led to decreased M1-polarized macrophages, corresponding with reduced alveolar bone resorption, uncovering a connection between subgingival microbiota alteration, macrophage M1 polarization, and alveolar bone resorption. Taken together, we showed that Caspase-11 fulfilled a crucial role in the noncanonical pyroptosis in PD, potentially influencing the subgingival microbiota and linking to M1 polarization, which was associated with alveolar bone resorption. These findings underscored the pivotal role of the Caspase-11-mediated noncanonical pyroptosis in PD pathogenesis and may provide critical insights into potential therapeutic avenues for mitigating PD.

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