Vitkov Ljubomir, Muñoz Luis E, Knopf Jasmin, Schauer Christine, Oberthaler Hannah, Minnich Bernd, Hannig Matthias, Herrmann Martin
Vascular & Exercise Biology Unit, Department of Biosciences, University of Salzburg, 5020 Salzburg, Austria.
Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, 66424 Homburg, Germany.
Int J Mol Sci. 2021 Apr 28;22(9):4647. doi: 10.3390/ijms22094647.
Periodontitis is considered a promoter of many systemic diseases, but the signaling pathways of this interconnection remain elusive. Recently, it became evident that certain microbial challenges promote a heightened response of myeloid cell populations to subsequent infections either with the same or other pathogens. This phenomenon involves changes in the cell epigenetic and transcription, and is referred to as ''trained immunity''. It acts via modulation of hematopoietic stem and progenitor cells (HSPCs). A main modulation driver is the sustained, persistent low-level transmission of lipopolysaccharide from the periodontal pocket into the peripheral blood. Subsequently, the neutrophil phenotype changes and neutrophils become hyper-responsive and prone to boosted formation of neutrophil extracellular traps (NET). Cytotoxic neutrophil proteases and histones are responsible for ulcer formations on the pocket epithelium, which foster bacteremia and endoxemia. The latter promote systemic low-grade inflammation (SLGI), a precondition for many systemic diseases and some of them, e.g., atherosclerosis, diabetes etc., can be triggered by SLGI alone. Either reverting the polarized neutrophils back to the homeostatic state or attenuation of neutrophil hyper-responsiveness in periodontitis might be an approach to diminish or even to prevent systemic diseases.
牙周炎被认为是许多全身性疾病的促进因素，但其这种内在联系的信号通路仍不清楚。最近，有证据表明，某些微生物刺激会增强髓样细胞群体对后续感染（无论是相同病原体还是其他病原体）的反应。这种现象涉及细胞表观遗传学和转录的变化，被称为“训练有素的免疫”。它通过调节造血干细胞和祖细胞（HSPCs）发挥作用。一个主要的调节驱动因素是脂多糖从牙周袋持续、持久地低水平进入外周血。随后，中性粒细胞表型发生变化，中性粒细胞变得反应过度，并易于促进中性粒细胞胞外陷阱（NET）的形成。细胞毒性中性粒细胞蛋白酶和组蛋白导致牙周袋上皮形成溃疡，从而促进菌血症和内毒素血症。后者会引发全身性低度炎症（SLGI），这是许多全身性疾病的一个先决条件，其中一些疾病，如动脉粥样硬化、糖尿病等，仅由SLGI即可引发。使极化的中性粒细胞恢复到稳态或减弱牙周炎中中性粒细胞的过度反应，可能是减少甚至预防全身性疾病的一种方法。
