The role of macrophages in the development of neuroinflammation in multiple sclerosis

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Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system with an autoimmune mechanism of development. It is known that along with T- and B-lymphocytes, cells of the innate immune system also play a significant role in the pathogenesis of MS. Macrophages are central to the functioning of the innate immune response and, depending on the phenotype, have pro-and anti-inflammatory properties. In the central nervous system, resident macrophages form microglia capable of presenting antigens and producing cytokines and, depending on phenotype, may participate in the development of autoimmune inflammation or maintaining immunological tolerance. The brief report presents data on the participation of macrophages in the pathogenesis of experimental autoimmune encephalomyelitis and MS. In addition, current methods of modulation of macrophage functions for the treatment of MS are discussed.

Keywords:

macrophages

microglia

neuroinflammation

multiple sclerosis

Authors:

Melnikov M.V.

Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency;
Pirogov Russian National Research Medical University;
National Research Center Institute of Immunology of the Federal Medical Biological Agency

SPIN RSCI: 6636-6419
Scopus AuthorID: 57221797118
ORCID: 0000-0001-6880-3668

Sviridova A.A.

Federal Center of Brain research and Neurotechnologies of the Federal Medical Biological Agency of Russia

SPIN RSCI: 6291-3236
Scopus AuthorID: 57209272018
ORCID: 0000-0003-1086-9052

Rogovskii V.S.

Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency;
Pirogov Russian National Research Medical University

ORCID: 0000-0002-3682-6571

Boyko A.N.

Pirogov Russian National Research Medical University;
Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency

SPIN RSCI: 9921-9109
Scopus AuthorID: 7102247663
ORCID: 0000-0002-2975-4151

Pashenkov M.V.

National Research Center Institute of Immunology of the Federal Medical Biological Agency of Russia

SPIN RSCI: 8690-0830
Scopus AuthorID: 56616259500
ORCID: 0000-0002-6995-1790

Received:

10.11.2021

Accepted:

26.11.2021

List of references:

Absinta M, Lassmann H, Trapp BD. Mechanisms underlying progression in multiple sclerosis. Curr Opin Neurol. 2020;33(3):277-285. https://doi.org/10.1097/WCO.0000000000000818
Boyko A, Kesselring J, Paty DW, et al. Multiple sclerosis and public health. Educational and management implications. World Health Organization, Department of Mental Health, Neuroscience and Neurological Disorders. 1999;(2):1-11.
Singh RP, Hasan S, Sharma S, et al. Th17 cells in inflammation and autoimmunity. Autoimmun Rev. 2014;13(12):1174-1181. https://doi.org/10.1016/j.autrev.2014.08.019
Reboldi A, Coisne C, Baumjohann D, et al. C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol. 2009;10(5):514-523. https://doi.org/10.1038/ni.1716
Sallusto F, Impellizzieri D, Basso C, et al. T-cell trafficking in the central nervous system. Immunol Rev. 2012;248(1):216-227. https://doi.org/10.1111/j.1600-065X.2012.01140.x
Moser T, Akgün K, Proschmann U, et al. The role of TH17 cells in multiple sclerosis: Therapeutic implications. Autoimmun Rev. 2020;19(10):102647. https://doi.org/10.1016/j.autrev.2020.102647
Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019;16(1):272. https://doi.org/10.1186/s12974-019-1674-2
Kemmerer CL, Pernpeintner V, Ruschil C, et al. Differential effects of disease modifying drugs on peripheral blood B cell subsets: A cross sectional study in multiple sclerosis patients treated with interferon-β, glatiramer acetate, dimethyl fumarate, fingolimod or natalizumab. PLoS One. 2020;15(7):e0235449. https://doi.org/10.1371/journal.pone.0235449
Sospedra M. B cells in multiple sclerosis. Curr Opin Neurol. 2018;31(3):256-262. https://doi.org/10.1097/WCO.000000000000563
Negron A, Stüve O, Forsthuber TG. Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control? Front Neurol. 2020;11:607766. https://doi.org/10.3389/fneur.2020.607766
Bell L, Lenhart A, Rosenwald A, et al. Lymphoid Aggregates in the CNS of Progressive Multiple Sclerosis Patients Lack Regulatory T Cells. Front Immunol. 2020;10:3090. https://doi.org/10.3389/fimmu.2019.03090
Polman CH, Dijkstra CD, Sminia T, Koetsier JC. Immunohistological analysis of macrophages in the central nervous system of Lewis rats with acute experimental allergic encephalomyelitis. J Neuroimmunol. 1986;11(3):215-222. https://doi.org/10.1016/0165-5728(86)90005-6
Brück W, Sommermeier N, Bergmann M, et al. Macrophages in multiple sclerosis. Immunobiology. 1996;195(4-5):588-600. https://doi.org/10.1016/S0171-2985(96)80024-6
Henderson AP, Barnett MH, Parratt JD, Prineas JW. Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann Neurol. 2009;66(6):739-753. https://doi.org/10.1002/ana.21800
Ponomarev ED, Shriver LP, Maresz K, Dittel BN. Microglial cell activation and proliferation precedes the onset of CNS autoimmunity. J Neurosci Res. 2005;81(3):374-389. https://doi.org/10.1002/jnr.20488
Nally FK, De Santi C, McCoy CE. Nanomodulation of Macrophages in Multiple Sclerosis. Cells. 2019;8(6):543. https://doi.org/10.3390/cells8060543
Ajami B, Bennett JL, Krieger C, et al. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci. 2011;14(9):1142-1149. https://doi.org/10.1038/nn.2887
Brosnan CF, Bornstein MB, Bloom BR. The effects of macrophage depletion on the clinical and pathologic expression of experimental allergic encephalomyelitis. J Immunol. 1981;126(2):614-620.
Huitinga I, van Rooijen N, de Groot CJ, et al. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med. 1990;172(4):1025-1033. https://doi.org/10.1084/jem.172.4.1025
Moreno MA, Burns T, Yao P, et al. Therapeutic depletion of monocyte-derived cells protects from long-term axonal loss in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2016;290:36-46. https://doi.org/10.1016/j.jneuroim.2015.11.004
Kornek B, Storch MK, Weissert R, et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol. 2000;157(1):267-276. https://doi.org/10.1016/S0002-9440(10)64537-3
Bitsch A, Schuchardt J, Bunkowski S, et al. Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain. 2000;123(Pt 6):1174-1183. https://doi.org/10.1093/brain/123.6.1174
Kuhlmann T, Lingfeld G, Bitsch A, et al. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain. 2002;125(Pt 10):2202-2212. https://doi.org/10.1093/brain/awf235
Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in acute multiple sclerosis lesions. Brain. 1997;120(Pt 3):393-399. https://doi.org/10.1093/brain/120.3.393
Bross M, Hackett, M, Bernitsas E. Approved and Emerging Disease Modifying Therapies on Neurodegeneration in Multiple Sclerosis. Int J Mol Sci. 2020;21(12):4312. https://doi.org/10.3390/ijms21124312
Tierney JB, Kharkrang M, La Flamme AC. Type II-activated macrophages suppress the development of experimental autoimmune encephalomyelitis. Immunol Cell Biol. 2009;87(3):235-240. https://doi.org/10.1038/icb.2008.99
Jiang HR, Milovanović M, Allan D, et al. IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages. Eur J Immunol. 2012;42(7):1804-1814. https://doi.org/10.1002/eji.201141947
Raine CS. Multiple sclerosis: The resolving lesion revealed. J Neuroimmunol. 2017;304:2-6. https://doi.org/10.1016/j.jneuroim.2016.05.021
Pul R, Moharregh-Khiabani D, Škuljec J, et al. Glatiramer acetate modulates TNF-α and IL-10 secretion in microglia and promotes their phagocytic activity. J Neuroimmune Pharmacol. 2011;6(3):381-388. https://doi.org/10.1007/s11481-010-9248-1
Kim HJ, Ifergan I, Antel JP, et al. Type 2 monocyte and microglia differentiation mediated by glatiramer acetate therapy in patients with multiple sclerosis. J Immunol. 2004;172(11):7144-7153. https://doi.org/10.4049/jimmunol.172.11.7144
Floris S, Ruuls SR, Wierinckx A, et al. Interferon-beta directly influences monocyte infiltration into the central nervous system. J Neuroimmunol. 2002;127(1-2):69-79. https://doi.org/10.1016/s0165-5728(02)00098-x
Waschbisch A, Sanderson N, Krumbholz M, et al. Interferon beta and vitamin D synergize to induce immunoregulatory receptors on peripheral blood monocytes of multiple sclerosis patients. PLoS One. 2014;9(12):e115488. https://doi.org/10.1371/journal.pone.0115488
Schilling S, Goelz S, Linker R, et al. Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration. Clin Exp Immunol. 2006;145(1):101-107. https://doi.org/10.1111/j.1365-2249.2006.03094.x
Schulze-Topphoff U, Varrin-Doyer M, et al. Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2. Proc Natl Acad Sci USA. 2016;113(17):4777-4782. https://doi.org/10.1073/pnas.1603907113
Diebold M, Sievers C, Bantug G, et al. Dimethyl fumarate influences innate and adaptive immunity in multiple sclerosis. J Autoimmun. 2018;86:39-50. https://doi.org/10.1016/j.jaut.2017.09.009
Ringheim GE, Lee L, Laws-Ricker L, et al. Teriflunomide attenuates immunopathological changes in the dark agouti rat model of experimental autoimmune encephalomyelitis. Front Neurol. 2013;4:169. https://doi.org/10.3389/fneur.2013.00169
Medina S, Sainz de la Maza S, Villarrubia N, et al. Teriflunomide induces a tolerogenic bias in blood immune cells of MS patients. Ann Clin Transl Neurol. 2019;6(2):355-363. https://doi.org/10.1002/acn3.711
Lewis ND, Haxhinasto SA, Anderson SM, et al. Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3. J Immunol. 2013;190(7):3533-3540. https://doi.org/10.4049/jimmunol.1201810
Di Dario M, Colombo E, Govi C, et al. Myeloid cells as target of fingolimod action in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e157. https://doi.org/10.1212/NXI.0000000000000157
Mindur JE, Ito N, Dhib-Jalbut S, Ito K. Early treatment with anti-VLA-4 mAb can prevent the infiltration and/or development of pathogenic CD11b+CD4+ T cells in the CNS during progressive EAE. PLoS One. 2014;9(6):e99068. https://doi.org/10.1371/journal.pone.0099068
Sucksdorff M, Tuisku J, Matilainen M, et al. Natalizumab treatment reduces microglial activation in the white matter of the MS brain. Neurol Neuroimmunol Neuroinflamm. 2019;6(4):e574. https://doi.org/10.1212/NXI.0000000000000574
Li R, Rezk A, Miyazaki Y, et al. Canadian B cells in MS Team. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Sci Transl Med. 2015;7(310):310ra166. https://doi.org/10.1126/scitranslmed.aab4176
Luessi F, Zipp F, Witsch E. Dendritic cells as therapeutic targets in neuroinflammation. Cell Mol Life Sci. 2016;73(13):2425-2450. https://doi.org/10.1007/s00018-016-2170-9
Correale J, Halfon MJ, Jack D, et al. Acting centrally or peripherally: A renewed interest in the central nervous system penetration of disease-modifying drugs in multiple sclerosis. Mult Scler Relat Disord. 2021;56:103264. https://doi.org/10.1016/j.msard.2021.103264
Carandini T, Cercignani M, Galimberti D, et al. The distinct roles of monoamines in multiple sclerosis: A bridge between the immune and nervous systems? Brain Behav Immun. 2021;94:381-391. https://doi.org/10.1016/j.bbi.2021.02.030
Malinova TS, Dijkstra CD, de Vries HE. Serotonin: A mediator of the gut-brain axis in multiple sclerosis. Mult Scler. 2018;24(9):1144-1150. https://doi.org/10.1177/1352458517739975
Shajib MS, Khan WI. The role of serotonin and its receptors in activation of immune responses and inflammation. Acta Physiol (Oxf). 2015;213(3):561-574. https://doi.org/10.1111/apha.12430
Durk T, Panther E, Muller T, et al. 5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes. Int Immunol. 2005;17(5):599-606.
de las Casas-Engel M, Dominguez-Soto A, Sierra-Filardi E, et al. Serotonin skews human macrophage polarization through HTR2B and HTR7. J Immunol. 2013;190(5):2301-2310.
Herr N, Bode C, Duerschmied D. The Effects of Serotonin in Immune Cells. Front Cardiovasc Med. 2017;4:48.
Nieto C, Rayo I, de Las Casas-Engel M, et al. Serotonin (5-HT) Shapes the Macrophage Gene Profile through the 5-HT2B-Dependent Activation of the Aryl Hydrocarbon Receptor. J Immunol. 2020;204(10):2808-2817. https://doi.org/10.4049/jimmunol.1901531
Szabo A, Gogolak P, Koncz G, et al. Immunomodulatory capacity of the serotonin receptor 5-HT2B in a subset of human dendritic cells. Sci Rep. 2018;8(1):1765. https://doi.org/10.1038/s41598-018-20173-y
Krivenko LV, Sviridova AA, Melnikov MV. et al. The effect of fluoxetine on the production of interleukin-6 and interleukin-1ß by dendritic cells in multiple sclerosis in vitro. Journal of Neurology and Psychiatry named after S.S. Korsakov. 2020;120(7-2):67-72. (In Russ.). https://doi.org/10.17116/jnevro202012007267
Belowski D, Kowalski J, Madej A, Herman ZS. Influence of antidepressant drugs on macrophage cytotoxic activity in rats. Pol J Pharmacol. 2004;56(6):837-842.
Du RH, Tan J, Sun XY, et al. Fluoxetine Inhibits NLRP3 Inflammasome Activation: Implication in Depression. Int J Neuropsychopharmacol. 2016;19(9):pyw037. https://doi.org/10.1093/ijnp/pyw037
Yoshioka Y, Sugino Y, Shibagaki F, et al. Dopamine attenuates lipopolysaccha-ride-induced expression of proinflammatory cytokines by inhibiting the nuclear translocation of NF-κB p65 through the for-mation of dopamine quinone in microglia. Eur J Pharmacol. 2020;866:172826. https://doi.org/10.1016/j.ejphar.2019.172826
Yan Y, Jiang W, Liu L, et al. Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell. 2015;160(1-2):62-73. https://doi.org/10.1016/j.cell.2014.11.047

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