Hajishengallis George, Chavakis Triantafyllos, Hajishengallis Evlambia, Lambris John D
Departments of *Microbiology and Preventive and Restorative Sciences, Division of Pediatric Dentistry, Penn Dental Medicine, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and Technische Universität Dresden, Faculty of Medicine, Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Germany
Departments of *Microbiology and Preventive and Restorative Sciences, Division of Pediatric Dentistry, Penn Dental Medicine, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and Technische Universität Dresden, Faculty of Medicine, Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Germany.
J Leukoc Biol. 2015 Oct;98(4):539-48. doi: 10.1189/jlb.3VMR1014-468R. Epub 2014 Dec 29.
Once viewed as simply antibacterial effector cells packed with antimicrobials, neutrophils are now increasingly appreciated for their regulatory roles in immunity and inflammation. The homeostatic regulation of neutrophils is thus crucial for optimal operation of the immune system. An attractive model to understand mechanistically the role of neutrophils is periodontitis, an oral inflammatory disease that is particularly sensitive to neutrophil alterations in numbers or function. The recruitment and proper activation of neutrophils are largely dependent on leukocyte integrins and complement. This review discusses how these processes are affected by host genetic or microbial factors leading to the development of periodontitis. For instance, both hypo- and hyper-recruitment of neutrophils as a result of deficiencies in the expression of β2 integrins or their negative regulators, respectively, causes unwarranted IL-17-dependent inflammatory bone loss. Moreover, microbial hijacking of C5aR (CD88) signaling in neutrophils impairs their antimicrobial function while promoting destructive inflammatory responses. These studies not only support the concept that neutrophil homeostasis is key to periodontal health but also reveal promising, new therapeutic targets as discussed in the review.
中性粒细胞曾一度被简单地视为充满抗菌物质的抗菌效应细胞，如今其在免疫和炎症中的调节作用越来越受到重视。因此，中性粒细胞的稳态调节对于免疫系统的最佳运作至关重要。牙周炎是一种对中性粒细胞数量或功能改变特别敏感的口腔炎症性疾病，是从机制上理解中性粒细胞作用的一个有吸引力的模型。中性粒细胞的募集和适当激活很大程度上依赖于白细胞整合素和补体。本综述讨论了这些过程如何受到导致牙周炎发展的宿主遗传或微生物因素的影响。例如，β2整合素表达缺陷或其负调节因子导致的中性粒细胞低募集和高募集，分别会导致不必要的依赖白细胞介素-17的炎症性骨质流失。此外，微生物劫持中性粒细胞中的C5aR（CD88）信号会损害其抗菌功能，同时促进破坏性炎症反应。这些研究不仅支持中性粒细胞稳态是牙周健康关键的概念，还揭示了如本综述中所讨论的有前景的新治疗靶点。
