Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, Germany.
Front Immunol. 2019 Jul 23;10:1724. doi: 10.3389/fimmu.2019.01724. eCollection 2019.
Chronic implant-related bone infections are a major problem in orthopedic and trauma-related surgery with severe consequences for the affected patients. As antibiotic resistance increases in general and because most antibiotics have poor effectiveness against biofilm-embedded bacteria in particular, there is a need for alternative and innovative treatment approaches. Recently, the immune system has moved into focus as the key player in infection defense and bone homeostasis, and the targeted modulation of the host response is becoming an emerging field of interest. The aim of this review was to summarize the current knowledge of impaired endogenous defense mechanisms that are unable to prevent chronicity of bone infections associated with a prosthetic or osteosynthetic device. The presence of foreign material adversely affects the immune system by generating a local immune-compromised environment where spontaneous clearance of planktonic bacteria does not take place. Furthermore, the surface structure of the implant facilitates the transition of bacteria from the planktonic to the biofilm stage. Biofilm formation on the implant surface is closely linked to the development of a chronic infection, and a misled adaption of the immune system makes it impossible to effectively eliminate biofilm infections. The interaction between the immune system and bone cells, especially osteoclasts, is extensively studied in the field of osteoimmunology and this crosstalk further aggravates the course of bone infection by shifting bone homeostasis in favor of bone resorption. T cells play a major role in various chronic diseases and in this review a special focus was therefore set on what is known about an ineffective T cell response. Myeloid-derived suppressor cells (MDSCs), anti-inflammatory macrophages, regulatory T cells (Ts) as well as osteoclasts all suppress immune defense mechanisms and negatively regulate T cell-mediated immunity. Thus, these cells are considered to be potential targets for immune therapy. The success of immune checkpoint inhibition in cancer treatment encourages the transfer of such immunological approaches into treatment strategies of other chronic diseases. Here, we discuss whether immune modulation can be a therapeutic tool for the treatment of chronic implant-related bone infections.
慢性植入物相关的骨感染是骨科和创伤相关手术中的一个主要问题，会给患者带来严重后果。由于抗生素耐药性的普遍增加，而且大多数抗生素对生物膜包裹的细菌的效果特别差，因此需要替代和创新的治疗方法。最近，免疫系统作为感染防御和骨稳态的关键因素引起了人们的关注，宿主反应的靶向调节正成为一个新兴的研究领域。本综述的目的是总结目前对无法预防与假体或内固定装置相关的慢性骨感染的内源性防御机制受损的认识。异物的存在通过产生局部免疫抑制环境来影响免疫系统，在这种环境中，浮游细菌不会自发清除。此外，植入物的表面结构促进了细菌从浮游状态向生物膜状态的转变。植入物表面生物膜的形成与慢性感染的发展密切相关，免疫系统的错误适应使得无法有效消除生物膜感染。免疫系统与骨细胞（尤其是破骨细胞）之间的相互作用在骨免疫学领域得到了广泛研究，这种串扰通过有利于骨吸收的方式使骨稳态发生转变，从而进一步加重了骨感染的进程。T 细胞在各种慢性疾病中发挥着重要作用，因此在本综述中特别关注了关于无效 T 细胞反应的已知内容。髓系来源的抑制细胞（MDSCs）、抗炎巨噬细胞、调节性 T 细胞（Ts）以及破骨细胞都抑制免疫防御机制并负调控 T 细胞介导的免疫。因此，这些细胞被认为是免疫治疗的潜在靶点。免疫检查点抑制在癌症治疗中的成功鼓励将这些免疫方法转移到其他慢性疾病的治疗策略中。在这里，我们讨论了免疫调节是否可以成为治疗慢性植入物相关骨感染的一种治疗工具。
