Parkinson disease (PD) is a progressive neurodegenerative disease that affects peripheral organs as well as the central nervous system and involves a fundamental role of neuroinflammation in its pathophysiology. Neurohistological and neuroimaging studies support the presence of ongoing and end-stage neuroinflammatory processes in PD. Moreover, numerous studies of peripheral blood and cerebrospinal fluid from patients with PD suggest alterations in markers of inflammation and immune cell populations that could initiate or exacerbate neuroinflammation and perpetuate the neurodegenerative process. A number of disease genes and risk factors have been identified as modulators of immune function in PD and evidence is mounting for a role of viral or bacterial exposure, pesticides and alterations in gut microbiota in disease pathogenesis. This has led to the hypothesis that complex gene-by-environment interactions combine with an ageing immune system to create the ‘perfect storm’ that enables the development and progression of PD. We discuss the evidence for this hypothesis and opportunities to harness the emerging immunological knowledge from patients with PD to create better preclinical models with the long-term goal of enabling earlier identification of at-risk individuals to prevent, delay and more effectively treat the disease.

帕金森病 (PD) 是一种进行性神经退行性疾病，影响外周器官和中枢神经系统，并涉及神经炎症在其病理生理学中的基本作用。神经组织学和神经影像学研究支持 PD 中存在正在进行的和终末期的神经炎症过程。此外，对 PD 患者外周血和脑脊液的大量研究表明，炎症标志物和免疫细胞群发生了改变，这些改变可能引发或加剧神经炎症并使神经退行性过程持续存在。许多疾病基因和风险因素已被确定为 PD 免疫功能的调节剂，并且越来越多的证据表明病毒或细菌暴露、杀虫剂和肠道微生物群的改变在疾病发病机制中的作用。这导致了这样一种假设，即复杂的基因与环境相互作用与老化的免疫系统相结合，创造了能够促进 PD 发展和进展的“完美风暴”。我们讨论了这一假设的证据以及利用 PD 患者新出现的免疫学知识来创建更好的临床前模型的机会，其长期目标是能够更早地识别高危个体以预防、延缓和更有效地治疗该疾病。