TLR-mediated activation of peripheral blood monocyte phagocytosis in patients with multiple sclerosis

Authors

DOI:

https://doi.org/10.14739/2310-1237.2020.2.212807

Keywords:

multiple sclerosis, IFN-β, phagocytic activity of monocytes, Toll-like receptors

Abstract

 

The aim of the study: to reveal peculiarities of the phagocytic activity of TLR4, TLR7/8-activated monocytes of peripheral blood, depending on the type of multiple sclerosis and clinical effectiveness of the treatment.

Material and methods. E. coli or ssRNA40/LyoVec lipopolysaccharide as TLR4 and TLR7/8 agonists were added to the monocyte-enriched cell suspension, respectively, and incubated for 24 hours at t 37 °C under an atmosphere of 5 % CO2. In parallel series, ram erythrocytes (RE) sensitized with hemolytic serum and inactivated C. albicans cells were used as phagocytosis objects; the incubation time was 30 minutes. The phagocytic index was calculated as the percentage of phagocytic monocytes and the phagocytic number as the ratio of the total number of absorbed REs or C. albicans cells to the number of monocytes that entered into phagocytosis.

The study presents the results of examination of 58 patients with recurring remitting (RRMS) and 36 patients with progressive (PMS) multiple sclerosis.

Results. The differences in the activation mechanisms of peripheral blood monocytes in patients with PC, which consist in different phagocytic activity in response to stimulation of TLR4 and TLR 7/8 depending on the disease conditions, were presented.

Phagocytic activity lesions of monocytes were observed both in patients with RRMS and PMS, associated mainly with FcR-mediated mechanisms of phagocytosis.

IFN-β therapy in patients with RRMS led to the correction of such disorders in patients with high treatment efficacy (responders), and TLR7/8-mediated activation of monocytes was accompanied by an increase in the number of phagocytic cells. In patients with low efficacy of IFN-β therapy (nonresponders), the nature of changes in the phagocytic activity of stimulated monocytes indicated a decrease in the functional reserve with regard to FcR-mediated phagocytosis.

Conclusions. The obtained results indicate differences in phagocytic activity indices during stimulation of TLR4 and TLR7/8 and may indicate the presence of functional and phenotypic alterations of peripheral blood monocytes depending on the effectiveness of MS treatment.

 

References

Baufeld, C., O'Loughlin, E., Calcagno, N., Madore, C., & Butovsky, O. (2018). Differential contribution of microglia and monocytes in neurodegenerative diseases. Journal of neural transmission, 125(5), 809-826. https://doi.org/10.1007/s00702-017-1795-7

Boyette, L. B., Macedo, C., Hadi, K., Elinoff, B. D., Walters, J. T., Ramaswami, B., Chalasani, G., Taboas, J. M., Lakkis, F. G., & Metes, D. M. (2017). Phenotype, function, and differentiation potential of human monocyte subsets. PloS one, 12(4), e0176460. https://doi.org/10.1371

Pinheiro, C., Monteiro, A., Dutra, F. F., Bozza, M. T., Peters-Golden, M., Benjamim, C. F., & Canetti, C. (2017). Short-Term Regulation of FcγR-Mediated Phagocytosis by TLRs in Macrophages: Participation of 5-Lipoxygenase Products. Mediators of inflammation, 2017, 2086840. https://doi.org/10.1155/2017/2086840

Gjelstrup, M. C., Stilund, M., Petersen, T., Møller, H. J., Petersen, E. L., & Christensen, T. (2018). Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis. Immunology and cell biology, 96(2), 160-174. https://doi.org/10.1111/imcb.1025

Jakubzick, C. V., Randolph, G. J., & Henson, P. M. (2017). Monocyte differentiation and antigen-presenting functions. Nature reviews. Immunology, 17(6), 349-362. https://doi.org/10.1038/nri.2017.28

Asadzadeh Manjili, F., Yousefi-Ahmadipour, A., & Kazemi Arababadi, M. (2020). The roles played by TLR4 in the pathogenesis of multiple sclerosis; A systematic review article. Immunology letters, 220, 63-70. https://doi.org/10.1016/j.imlet.2020.02.004

Zheng, C., Chen, J., Chu, F., Zhu, J., & Jin, T. (2020). Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis. Frontiers in molecular neuroscience, 12, 314. https://doi.org/10.3389/fnmol.2019.00314

Bhargava, P., Nogueras-Ortiz, C., Chawla, S., Bæk, R., Jørgensen, M. M., & Kapogiannis, D. (2019). Altered Levels of Toll-Like Receptors in Circulating Extracellular Vesicles in Multiple Sclerosis. Cells, 8(9), 1058. https://doi.org/10.3390/cells8091058

Deckx, N., Willekens, B., Wens, I., Eijnde, B. O., Goossens, H., Van Damme, P., Berneman, Z. N., & Cools, N. (2016). Altered molecular expression of TLR-signaling pathways affects the steady-state release of IL-12p70 and IFN-α in patients with relapsing-remitting multiple sclerosis. Innate immunity, 22(4), 266-273. https://doi.org/10.1177/1753425916642615

Bender, A. T., Tzvetkov, E., Pereira, A., Wu, Y., Kasar, S., Przetak, M. M., Vlach, J., Niewold, T. B., Jensen, M. A., & Okitsu, S. L. (2020). TLR7 and TLR8 Differentially Activate the IRF and NF-κB Pathways in Specific Cell Types to Promote Inflammation. ImmunoHorizons, 4(2), 93-107. https://doi.org/10.4049/immunohorizons.2000002

Golden, R. (2018). A Review of Multiple Sclerosis Treatments: Interferon Beta, Glatiramer Acetate, Fingolimod, and Natalizumab. Biology and Microbiology Graduate Students Plan B Research Projects. 3. https://openprairie.sdstate.edu/biomicro_plan-b/3

Chuluundorj, D., Harding, S. A., Abernethy, D., & La Flamme, A. C. (2017). Glatiramer acetate treatment normalized the monocyte activation profile in MS patients to that of healthy controls. Immunology and cell biology, 95(3), 297-305. https://doi.org/10.1038/icb.2016.99

Kzhyshkowska, J., Gudima, A., Moganti, K., Gratchev, A., & Orekhov, A. (2016). Perspectives for Monocyte/Macrophage-Based Diagnostics of Chronic Inflammation. Transfusion medicine and hemotherapy, 43(2), 66-77. https://doi.org/10.1159/000444943

Bustamante, M. F., Morcillo-Suárez, C., Malhotra, S., Rio, J., Leyva, L., Fernández, O., … Comabella, M. (2015). Pharmacogenomic study in patients with multiple sclerosis. Neurology - Neuroimmunology Neuroinflammation, 2(5), e154. https://doi.org/10.1212/nxi.0000000000000154

Editors: Rousselet, G. (Ed.) (2018). Macrophages. Methods and Protocols. In Methods in Molecular Biology. Humana Press. https://doi.org/10.1007/978-1-4939-7837-3

Metcalf, T. U., Wilkinson, P. A., Cameron, M. J., Ghneim, K., Chiang, C., Wertheimer, A. M., Hiscott, J. B., Nikolich-Zugich, J., & Haddad, E. K. (2017). Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists. Journal of immunology (Baltimore, Md. : 1950), 199(4), 1405-1417. https://doi.org/10.4049/jimmunol.1700148

González-Oria, M. C., Márquez-Coello, M., Girón-Ortega, J. A., Argente, J., Moya, M., & Girón-González, J. A. (2019). Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 14(3), 413-422. https://doi.org/10.1007/s11481-018-09832-z

Waschbisch, A., Schröder, S., Schraudner, D., Sammet, L., Weksler, B., Melms, A., Pfeifenbring, S., Stadelmann, C., Schwab, S., & Linker, R. A. (2016). Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System. Journal of immunology (Baltimore, Md. : 1950), 196(4), 1558-1567. https://doi.org/10.4049/jimmunol.1501960

Hurtado-Guerrero, I., Pinto-Medel, M. J., Urbaneja, P., Rodriguez-Bada, J. L., León, A., Guerrero, M., Fernández, Ó., Leyva, L., & Oliver-Martos, B. (2017). Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß. PloS one, 12(1), e0170031. https://doi.org/10.1371/journal.pone.0170031

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1.
Skliar AI, Koliada OМ, Vdovichenko NІ, Koliada TI. TLR-mediated activation of peripheral blood monocyte phagocytosis in patients with multiple sclerosis. Pathologia [Internet]. 2020Sep.28 [cited 2024Dec.23];(2). Available from: http://pat.zsmu.edu.ua/article/view/212807

Issue

No. 2 (2020)

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Original research

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