Department of Orthopaedic Surgery, Cleveland Clinic Adult Reconstruction Research (CCARR), Cleveland Clinic, Cleveland, Ohio, USA.
Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA.
J Orthop Res. 2024 Jan;42(1):7-20. doi: 10.1002/jor.25723. Epub 2023 Nov 4.
Periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. Even with current treatments, failure rates are unacceptably high with a 5-year mortality rate of 26%. Majority of the literature in the field has focused on development of better biomarkers for diagnostics and treatment strategies including innovate antibiotic delivery systems, antibiofilm agents, and bacteriophages. Nevertheless, the role of the immune system, our first line of defense during PJI, is not well understood. Evidence of infection in PJI patients is found within circulation, synovial fluid, and tissue and include numerous cytokines, metabolites, antimicrobial peptides, and soluble receptors that are part of the PJI diagnosis workup. Macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) are initially recruited into the joint by chemokines and cytokines produced by immune cells and bacteria and are activated by pathogen-associated molecular patterns. While these cells are efficient killers of planktonic bacteria by phagocytosis, opsonization, degranulation, and recruitment of adaptive immune cells, biofilm-associated bacteria are troublesome. Biofilm is not only a physical barrier for the immune system but also elicits effector functions. Additionally, bacteria have developed mechanisms to evade the immune system by inactivating effector molecules, promoting killing or anti-inflammatory effector cell phenotypes, and intracellular persistence and dissemination. Understanding these shortcomings and the mechanisms by which bacteria can subvert the immune system may open new approaches to better prepare our own immune system to combat PJI. Furthermore, preoperative immune system assessment and screening for dysregulation may aid in developing preventative interventions to decrease PJI incidence.
假体周围关节感染（PJI）是全关节置换术的主要并发症。即使采用当前的治疗方法，失败率仍然很高，5 年死亡率为 26%。该领域的大多数文献都集中在开发更好的生物标志物用于诊断和治疗策略，包括创新的抗生素输送系统、抗生物膜剂和噬菌体。然而，免疫系统在 PJI 中的作用，即我们的第一道防线，尚未得到很好的理解。在 PJI 患者的感染证据中，在循环、滑液和组织中发现了许多细胞因子、代谢物、抗菌肽和可溶性受体，它们是 PJI 诊断的一部分。巨噬细胞、中性粒细胞和髓样来源的抑制细胞（MDSCs）最初通过免疫细胞和细菌产生的趋化因子和细胞因子被招募到关节中，并被病原体相关分子模式激活。虽然这些细胞通过吞噬作用、调理作用、脱颗粒作用和适应性免疫细胞的募集有效地杀死浮游细菌，但生物膜相关细菌是个麻烦。生物膜不仅是免疫系统的物理屏障，还会引发效应功能。此外，细菌已经发展出逃避免疫系统的机制，包括使效应分子失活、促进杀伤或抗炎效应细胞表型以及细胞内持续存在和传播。了解这些缺陷以及细菌可以颠覆免疫系统的机制，可能为更好地准备我们自己的免疫系统来对抗 PJI 开辟新的方法。此外，术前免疫系统评估和失调筛查可能有助于开发预防干预措施，以降低 PJI 的发生率。
