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来源于被牙周致病菌福赛拟杆菌感染的巨噬细胞的细胞外囊泡的蛋白质组和免疫应答。

Proteome and immune responses of extracellular vesicles derived from macrophages infected with the periodontal pathogen Tannerella forsythia.

机构信息

Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.

Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.

出版信息

J Extracell Vesicles. 2023 Dec;12(12):e12381. doi: 10.1002/jev2.12381.

DOI:10.1002/jev2.12381
PMID:38014595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10682907/
Abstract

Periodontitis is a chronic inflammatory disease caused by periodontal pathogens in subgingival plaque and is associated with systemic inflammatory diseases. Extracellular vesicles (EVs) released from host cells and pathogens carry a variety of biological molecules and are of interest for their role in disease progression and as diagnostic markers. In the present study, we analysed the proteome and inflammatory response of EVs derived from macrophages infected with Tannerella forsythia, a periodontal pathogen. The EVs isolated from the cell conditioned medium of T. forsythia-infected macrophages were divided into two distinct vesicles, macrophage-derived EVs and T. forsythia-derived OMVs, by size exclusion chromatography combined with density gradient ultracentrifugation. Proteome analysis showed that in T. forsythia infection, macrophage-derived EVs were enriched with pro-inflammatory cytokines and inflammatory mediators associated with periodontitis progression. T. forsythia-derived OMVs harboured several known virulence factors, including BspA, sialidase, GroEL and various bacterial lipoproteins. T. forsythia-derived OMVs induced pro-inflammatory responses via TLR2 activation. In addition, we demonstrated that T. forsythia actively released OMVs when T. forsythia encountered macrophage-derived soluble molecules. Taken together, our results provide insight into the characterisation of EVs derived from cells infected with a periodontal pathogen.

摘要

牙周炎是一种由龈下菌斑中牙周病原体引起的慢性炎症性疾病，与全身炎症性疾病有关。宿主细胞和病原体释放的细胞外囊泡（EVs）携带多种生物分子，因其在疾病进展中的作用和作为诊断标志物的潜力而受到关注。在本研究中，我们分析了感染牙周病原体福赛坦纳菌的巨噬细胞衍生的 EVs 的蛋白质组和炎症反应。通过大小排阻色谱结合密度梯度超速离心，将源自 T. forsythia 感染巨噬细胞细胞条件培养基的 EVs 分为两种不同的囊泡，即巨噬细胞衍生的 EVs 和 T. forsythia 衍生的 OMVs。蛋白质组分析表明，在 T. forsythia 感染中，巨噬细胞衍生的 EVs 富含与牙周病进展相关的促炎细胞因子和炎症介质。T. forsythia 衍生的 OMVs 携带几种已知的毒力因子，包括 BspA、唾液酸酶、GroEL 和各种细菌脂蛋白。T. forsythia 衍生的 OMVs 通过 TLR2 激活诱导促炎反应。此外，我们证明当 T. forsythia 遇到巨噬细胞衍生的可溶性分子时，T. forsythia 会主动释放 OMVs。总之，我们的研究结果深入了解了感染牙周病原体的细胞衍生的 EVs 的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/6353a13bb757/JEV2-12-12381-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/2b09290ae59e/JEV2-12-12381-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/2bc3f30fe161/JEV2-12-12381-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/55f092490c01/JEV2-12-12381-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/86d2bd9f8c05/JEV2-12-12381-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/18cde12b1593/JEV2-12-12381-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/a03790418beb/JEV2-12-12381-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/6353a13bb757/JEV2-12-12381-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/2b09290ae59e/JEV2-12-12381-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/2bc3f30fe161/JEV2-12-12381-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/55f092490c01/JEV2-12-12381-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/86d2bd9f8c05/JEV2-12-12381-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/18cde12b1593/JEV2-12-12381-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/a03790418beb/JEV2-12-12381-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/10682907/6353a13bb757/JEV2-12-12381-g006.jpg

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