Monocyte Function in Parkinson's Disease and the Impact of Autologous Serum on Phagocytosis
Open accessAbstract
Background - Increasing evidence implicates involvement of the innate immune system in the initiation and progression of Parkinson’s disease (PD). Monocytes and monocyte-derived cells perform a number of functions such as phagocytosis, chemotaxis and cytokine secretion, which may be particularly relevant to PD pathology. The behaviour of these cells in early-moderate disease, in conditions more similar to the in-vivo environment has not been fully evaluated. Research Question – Does monocyte function, including phagocytosis, chemotaxis and cytokine secretion, differ in early-moderate PD compared to age and gender-matched controls? Methods - Participants included PD patients (n=41) with early-moderate stage disease (Hoehn and Yahr ≤ 2) and age and gender matched controls (n=41). Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and monocytes were further separated using CD14 magnetic beads. Functional assays, including bead phagocytosis (in standard medium and autologous serum), Boyden chamber trans-well chemotaxis, and cytokine secretion on lipopolysaccharide stimulation were performed. Monocyte surface markers relating to chemotaxis were measured using immunohistochemistry and flow cytometry. Between-group analysis was performed using paired t-tests. Results – An autologous serum environment significantly increased bead phagocytosis compared to standard medium as expected, in both patients and controls. When in autologous serum, PD monocytes demonstrated enhanced phagocytosis compared to control monocytes (p=0.029). The level of serum-based phagocytosis was influenced by complement inactivation and the origin of the serum. There were no significant differences between PD and controls in terms of standard medium based monocyte migration or cytokine secretion in this cohort. Conclusions - Autologous serum has a significant influence on monocyte phagocytosis and reveals increased phagocytic capacity in early-moderate PD compared to controls. These conditions may better reflect the function of monocytes in-vivo in PD patients than standard medium based phagocytosis assays. Further studies will be required to replicate these results in larger cohorts, including earlier and later stages of disease, and to understand which serum factors are responsible for this observation and the potential mechanistic relevance to PD pathogenesis.
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Peripheral monocytes have been shown to enhance phagocytosis in autologous serum of patients with Parkinson's disease, supporting the involvement of innate immunity.
“Peripheral monocytes have been shown to enhance phagocytosis in autologous serum of patients with Parkinson's disease, supporting the involvement of innate immunity.84”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [84]
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Huang, B., Zhenxin, Y., Chen, S., Tan, Z., Zong, Z., Zhang, H., & Xiong, X. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/1315248 · Cited by 19 · see citing works
“Several studies have demonstrated an enrichment of classical monocytes in peripheral blood of PD patients, especially in those with a high risk of developing early dementia (HR-PD), of which monocytes express higher levels of TREM2 [88, 89].”
Glial cell crosstalk in Parkinson's disease: Mechanisms, implications, and therapeutic strategies
Wang, N., Xiao, X., Chen, Z., Xu, K., Cao, X., Kou, D., & Zeng, J. (2025) · Fundamental Research · doi:10.1016/j.fmre.2024.12.023 · Cited by 17 · see citing works
“Subsequent research has identified upregulated levels of monocytes and their precursor cells in the peripheral blood of PD patients [ 60 ].”
Gu, B., Huang, X., Avula, P. K., Caruso, E., Drysdale, C., Vessey, K. A., Ou, A., Fowler, C., Liu, T.-H., Lin, Y., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.634177 · Cited by 14 · see citing works
Jiao, F., Zhou, L., & Wu, Z. (2024) · Neurological Sciences · doi:10.1007/s10072-024-07878-x · Cited by 13 · see citing works
Bernardino, L. I. (2021) · Current topics in behavioral neurosciences · doi:10.1007/7854_2021_235 · Cited by 17 · see citing works
Autophagy Process in Parkinson’s Disease Depends on Mutations in the GBA1 and LRRK2 Genes
Bezrukova, A. I., Basharova, K. S., Emelyanov, A., Rybakov, A. V., Miliukhina, I. V., Пчелина, С. Н., & Usenko, T. S. (2025) · Biochemical Genetics · doi:10.1007/s10528-025-11125-z · Cited by 8 · see citing works
Herbst, A. C., Reedy, S. E., Page, A. E., Horohov, D. W., & Adams, A. A. (2022) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2022.110459 · Cited by 10 · see citing works
Hattori, A., Ohta, E., Nagai, M., Iwabuchi, K., & Okano, H. (2021) · Methods · doi:10.1016/j.ymeth.2021.04.019 · Cited by 8 · see citing works
Trained immunity in acute and chronic neurological diseases
Zhang, S., & Liesz, A. (2026) · eLife · doi:10.7554/elife.106037 · Cited by 6 · see citing works
“…early-stage PD patients have been shown to exhibit altered phagocytic capacity depending on culture conditions, with greater phagocytosis observed under more physiologically relevant conditions, highlighting the importance of context in assessing immune function in PD ( Wijeyekoon et al., 2018 ).”
Navarro, E., Udine, E., Lopes, K. D. P., Parks, M., Riboldi, G., Schilder, B., Humphrey, J., Snijders, G. J. L., Vialle, R., Zhuang, M.-J., et al. (2020) · bioRxiv · doi:10.1101/2020.07.20.212407 · Cited by 3
Lill, C., di Flora, A., Sechi, L., Pereira, F. C., Moisoi, N., Nikolovski, N., Aktekin, M., Gursoy-Ozdemir, Y., Deecke, L., Cossu, D., et al. (2025) · Aging and Disease · doi:10.14336/ad.2024.1163 · Cited by 2
“Finally, Wijeyekoon et al. [133] did not observe any differences in response to LPS (1ng/ml, 24h-incubation) when measuring cytokine secretion using an electrochemiluminescence assay.”
Fu, R.-N., Lian, W., Zhang, B.-H., Liu, G., Feng, X.-Y., Zhu, Y.-J., Zhou, J.-A., Zhang, X.-Y., Wang, S.-K., Huo, H.-J., et al. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s481649 · Cited by 2 · see citing works
“35 Platelets actively participate in inflammatory processes through their mediation of leukocyte adhesion and extravasation.”
Neuroinflammation and Immune Dysfunction in the Mechanisms of Development of Parkinson’s Disease
Idova, G. V., Лазаревна, А. Е., & Zhanaeva, S. Y. (2023) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-023-01549-8 · Cited by 2 · see citing works
“However, despite the increased expression of TLR4 on these cells, serum α -syn clearance did not change, indicating a selective de fi ciency or suppression of α -syn uptake [Wijeyekoon et al., 2018; Harms et al., 2021].”
Porel, P., Varish, G., & Aran, K. R. (2025) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-025-01875-3 · Cited by 1 · see citing works
Sun, Y.-Z., Bai, Z., & Wang, Z.-Y. (2025) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2025.108018 · Cited by 1 · see citing works
NEUROINFLAMMATION AND IMMUNE DYSFUNCTION IN THE PATHOGENESIS OF PARKINSON’S DISEASE
Idova, G. V., Лазаревна, А. Е., & Zhanaeva, S. Y. (2023) · Журнал высшей нервной деятельности им И П Павлова · doi:10.31857/s0044467723040056 · Cited by 1 · see citing works
Immune response during idiopathic Parkinson's disease: From humans to animal models
Nissen, S. K., Ferreira, S. A., Klæstrup, I. H., & Romero‐Ramos, M. (2021) · International review of movement disorders · doi:10.1016/bs.irmvd.2021.08.006 · Cited by 1 · see citing works
Lin, K., Wang, P., Li, S., Ma, C., Wen, D., Wang, X., & Liao, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1712425
“Research in Parkinson ’ s Disease (PD) has shown improved phagocytic function in monocytes (157), with disease occurrence linked to increased monocyte brain in fi l-tration (158).”
Paul, K., Wilkins, O. M., Carloni, E., Fikse, E. N., Salas, L. A., Lee, S., Feldman, M. S., Thompson, R., Kersey, G. E., Jeffreys, C. A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.30.715379
Indirubin and Retinoic Acid Show Binding Affinity to Monocyte Biomarker CSF3R in Parkinson's Disease
Bao, Z., Zhi, S., & Jie, M. (2026) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.70197 · Cited by 1 · see citing works
“Monocyte is a prime constituent of the peripheral innate immune system with numerous imperative functions (like phagocytosis, chemotaxis, and cytokine secretion) [20, 21].”
A Seven-Gene Signature for the Diagnosis of Parkinson’s Disease and Immune Infiltration Analysis
Wei, C., Xue, R., Gao, Z., Zhu, H., & Xu, X. (2025) · Twin Research and Human Genetics · doi:10.1017/thg.2025.10008
“Accumulated evidence indicates that both cellular and humoral immune responses are altered in PD patients (Kustrimovic et al., 2018; Wijeyekoon et al., 2018).”
Vitola, P. L. (2020) · doi:10.21954/ou.ro.000111c4
“Monocytes are a subset of myeloid cells which represent the main component of the peripheral innate immune system (Wijeyekoon et al., 2018; Mahad et al., 2006).”
Background
- Authors
- Wijeyekoon, R. S., Kronenberg-Versteeg, D., Scott, K. M., Hayat, S., Jones, J. L., Clatworthy, M. R., Floto, R. A., Barker, R. A., & Williams-Gray, C. H.
- Affiliations
- University of Cambridge (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Corresponding author
- Wijeyekoon, Ruwani S.
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2018-10-16
- Volume
- 9
- Pages
- 870-870
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC6198066
- OpenAlex
- W2896610227
- Cited by
- 50
- References
- 34
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 13 · 2020: 2 · 2019: 2
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Apollo (cc-by)
- Funders
- Medical Research Council
- Addenbrooke's Charitable Trust, Cambridge University Hospitals
- Rosetrees Trust
- Wellcome Trust
- National Institute for Health Research
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, monocytes, phagocytosis, autologous serum, chemotaxis, cytokine production, innate immunity, complement inactivation, monocyte migration, peripheral blood mononuclear cells
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