Periodontitis is a chronic inflammatory infectious disease that affects the integrity of tooth-supporting tissues and has adverse systemic consequences. Advances in sequencing technologies have uncovered organisms that are exclusively found in high numbers in periodontal lesions, such as the gram-positive anaerobic rod, Filifactor alocis. F. alocis can manipulate neutrophil effector functions, which allows the organism to survive within these granulocytes. Several neutrophil functions have been tested in the context of F. alocis challenge, but the effect of the organism on neutrophil apoptosis is still unknown. RNA sequencing of human neutrophils challenged with F. alocis showed that apoptosis pathways were differentially regulated. Compared to media-cultured controls, F. alocis-challenged neutrophils maintain their nuclear morphology, do not stain for Annexin V or 7-AAD, and have decreased DNA fragmentation. Inhibition of apoptosis by F. alocis involved reduced caspase-3, −8, and − 9 activation and upregulation of important anti-apoptotic proteins. Prolonged lifespan was dependent on contact through TLR2/6, and F. alocis-challenged neutrophils retained their functional capacity to induce inflammation for longer timepoints. This is the first in-depth characterization of neutrophil apoptotic programs in response to an oral pathogen and provides key information on how bacteria manipulate immune cell mechanisms to maintain a dysregulated inflammatory response.

中文翻译：

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新兴的口腔病原体 Filifactor alocis 延长了人类中性粒细胞的功能寿命

牙周炎是一种慢性炎症性传染病，会影响牙齿支持组织的完整性，并具有不良的全身后果。测序技术的进步发现了仅在牙周病变中大量发现的生物体，例如革兰氏阳性厌氧杆，Filifactor alocis。F. alocis可以操纵中性粒细胞效应器功能，从而使生物体在这些粒细胞内存活。已经在F. alocis挑战的背景下测试了几种中性粒细胞功能，但该生物体对中性粒细胞凋亡的影响仍然未知。用F. alocis挑战的人类中性粒细胞的 RNA 测序表明细胞凋亡途径受到不同的调节。与培养基培养的对照相比，F. alocis攻击的中性粒细胞保持其核形态，不染色膜联蛋白 V 或 7-AAD，并且 DNA 片段化减少。F. alocis对细胞凋亡的抑制涉及减少 caspase-3、-8 和 -9 的激活和重要的抗细胞凋亡蛋白的上调。延长寿命取决于通过 TLR2/6 和F. alocis的接触受攻击的中性粒细胞在更长的时间点保持其诱导炎症的功能能力。这是响应口腔病原体的中性粒细胞凋亡程序的首次深入表征，并提供了有关细菌如何操纵免疫细胞机制以维持失调的炎症反应的关键信息。