Porphyromonas gingivalis and Its Outer Membrane Vesicles Induce Neuroinflammation in Mice Through Distinct Mechanisms

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease Pub Date : 2025-02-11 DOI:10.1002/iid3.70135

Yu Qiu, Yueyang Zhao, Guiqiong He, Deqin Yang

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引用次数: 0

Abstract

Background

Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder, with neuroinflammation playing an important role in its progression to become a major research focus. The role of Porphyromonas gingivalis (Pg) and its outer membrane vesicles (Pg OMVs) in AD development is uncertain, particularly regarding their effects on neuroinflammation.

Methods

The cognition of mice injected with Pg, Pg OMVs, or PBS via the tail vein was assessed by the Morris water maze test. Pathological changes in the mouse brain were analyzed via immunohistochemistry, immunofluorescence and hematoxylin‒eosin (H&E) staining, and the ultrastructure of the hippocampus was observed via transmission electron microscopy (TEM). Plasma levels of inflammatory factors were assessed by enzyme-linked immunosorbent assay (ELISA). Protein levels of brain inflammatory factor, occludin, and NLRP3 inflammasome-related proteins were assessed by western blotting.

Results

Memory impairment; notable neuroinflammation, including astrocyte and microglial activation; and elevated protein levels of IL-1β, TNF-α, and IL-6 in the hippocampus were detected in the Pg and Pg OMV groups. However, Pg induced weight loss and systemic inflammation, such as splenomegaly and increased IL-1β and TNF-α levels in plasma, whereas Pg OMVs had minimal impact. In addition, Pg induced more pronounced activation of the NLRP3 inflammasome compared to Pg OMVs. In contrast, only the Pg OMV group exhibited blood−brain barrier (BBB) disruption characterized by reduced integrity of tight junctions and lower levels of occludin protein.

Conclusions

Pg is associated with a significant immune response and systemic inflammation, which in turn exacerbates neuroinflammation via activating NLRP3 inflammasome. However, Pg OMVs might elude the systemic immune response and disrupt tight junctions, thereby entering the brain and directly triggering neuroinflammation.

Abstract Image

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牙龈卟啉单胞菌及其外膜囊泡通过不同机制诱导小鼠神经炎症

阿尔茨海默病（Alzheimer's disease， AD）是最常见的慢性神经退行性疾病，神经炎症在其发展过程中起着重要作用，已成为研究热点。牙龈卟啉单胞菌（Pg）及其外膜囊泡（Pg OMVs）在AD发展中的作用尚不确定，特别是关于它们对神经炎症的影响。方法采用Morris水迷宫法测定经尾静脉注射Pg、Pg omv或PBS小鼠的认知能力。通过免疫组织化学、免疫荧光和苏木精-伊红（H&；E）染色分析小鼠大脑的病理变化，透射电镜（TEM）观察海马的超微结构。采用酶联免疫吸附试验（ELISA）评估血浆炎症因子水平。western blotting检测脑炎症因子、occludin和NLRP3炎性小体相关蛋白水平。结果：记忆障碍；显著的神经炎症，包括星形胶质细胞和小胶质细胞活化；Pg和Pg OMV组海马组织中IL-1β、TNF-α、IL-6蛋白水平升高。然而，Pg诱导体重减轻和全身炎症，如脾肿大和血浆中IL-1β和TNF-α水平升高，而Pg omv的影响很小。此外，与Pg omv相比，Pg诱导NLRP3炎症小体的激活更为明显。相比之下，只有Pg OMV组表现出血脑屏障（BBB）破坏，其特征是紧密连接完整性降低和occludin蛋白水平降低。Pg与显著的免疫反应和全身性炎症相关，这反过来又通过激活NLRP3炎性体加剧神经炎症。然而，Pg omv可能会避开全身免疫反应并破坏紧密连接，从而进入大脑并直接引发神经炎症。

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来源期刊

Immunity, Inflammation and Disease Medicine-Immunology and Allergy

CiteScore

3.60

自引率

0.00%

发文量

146

审稿时长

8 weeks

期刊介绍： Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology