Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Dysregulation of peripheral monocytes and pro-inflammation of alpha-synuclein in Parkinson's disease.

Abstract

BACKGROUND AND OBJECTIVES: Mounting evidence indicates the involvement of the innate immune system in Parkinson's disease (PD). Nevertheless, the implications of peripheral monocytes have not been fully elucidated. Although alpha-synuclein (alpha-synuclein) has been described as a pathological hallmark of PD, the proinflammatory effect of alpha-synuclein on monocytes is understudied. This study aimed to comprehensively characterize peripheral monocytes in PD patients and to investigate the proinflammatory magnitude of fibrillar alpha-synuclein. METHODS: Using flow cytometry, we explored the distribution of monocytic subpopulations. We also investigated the actions of peripheral monocytes in response to lipopolysaccharides (LPS) and to fibrillar alpha-synuclein stimuli by measuring inflammatory molecule levels in post-culture supernatants. RESULTS: Classical monocytes were enriched, in parallel with lower proportions of intermediate and nonclassical monocytes in patients with PD than in controls. Lower levels of TNF-alpha and IL-6 were spontaneously produced by unstimulated monocytes in patients with PD. LPS and fibrillar alpha-synuclein stimuli induced high levels of TNF-alpha, IL-1beta, IL-6, and sCD163 in the PD and control groups. Strikingly, the fold induction of TNF-alpha and IL-6 was lower in patients with PD than that in normal controls under the same stimulation. CONCLUSION: Our results revealed a strong dysregulation of peripheral monocytes in PD patients, including subpopulation shifts and impaired response to specific stimuli, and the proinflammatory effect of alpha-synuclein on monocytes. Further studies are needed to clarify the specific mechanisms by which these immunological abnormalities are present in PD to open the possibility of immunoregulatory therapy.