Current progress on the role of central nervous system boarder-associated macrophages in brain homeostasis and diseases

doi:10.16098/j.issn.0529-1356.2024.04.004

Abstract

Abstract:

An increasing number of studies have been focused on the field of immune system in the central nervous system（CNS），as the viewpoint of CNS immune privilege being challenged. Among them, CNS boarder-associated macrophages（BAMs）play a prominent role in the regulation of brain homeostasis and related diseases. Unlike microglia located in the brain parenchyma, BAMs are a type of specialized macrophages located in the meninges (including dura, arachnoid, and leptomeninges) ,perivascular spaces, and choroid plexus. They are crucial for immune surveillance, cerebrospinal fluid drainage, antigen clearance, material exchange, and etc. Here, we reviewed a series of relevant studies on the origin and roles of BAMs in CNS, so as to broaden the understanding of the mechanisms of by which BAMs maintain the brain homeostasis, as well as provide novel insights into the treatment of CNS diseases including Alzheimer 's disease.

Key words: Central nervous system, Boarder-associated macrophage, Cerebrospinal fluid circulation, Homeostasis regulation, Central nervous system diseases

CLC Number:

R392
R741

SHAO Chen-shuo WEI Li-hang TAN Guo-he. Current progress on the role of central nervous system boarder-associated macrophages in brain homeostasis and diseases[J]. Acta Anatomica Sinica, 2024, 55(4): 399-406.

References

［1］Mundt S, Greter M, Becher B. The CNS mononuclear phagocyte system in health and disease ［J］. Neuron, 2022, 110(21): 3497-3512.

［2］Castellani G, Croese T, Peralta Ramos JM, et al. Transforming the understanding of brain immunity ［J］. Science, 2023, 380(6640): eabo7649.

［3］Drieu A, Du S, Storck SE, et al. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid ［J］. Nature, 2022, 611(7936): 585-593.

［4］Sun R, Jiang H. Border-associated macrophages in the central nervous system ［J］. J Neuroinflammation, 2024,21(1):67.

［5］Kierdorf K, Masuda T, Jordo MJC, et al. Macrophages at CNS interfaces: ontogeny and function in health and disease ［J］. Nat Rev Neurosci, 2019, 20(9): 547-562.

［6］Zhilei B, Yandong G, Tao H, et al. Deciphering human macrophage development at single-cell resolution ［J］. Nature, 2020, 582(7813): 571-576.

［7］Ginhoux F, Greter M, Leboeuf M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages ［J］. Science, 2010, 330(6005): 841-845.

［8］Goldmann T, Wieghofer P, Jordão MJ, et al. Origin, fate and dynamics of macrophages at central nervous system interfaces ［J］. Nat Immunol, 2016, 17(7): 797-805.

［9］Masuda T, Amann L, Monaco G, et al. Specification of CNS macrophage subsets occurs postnatally in defined niches ［J］. Nature, 2022, 604(7907): 740-748.

［10］Utz SG, See P, Mildenberger W, et al. Early fate defines microglia and non-parenchymal brain macrophage development ［J］. Cell, 2020, 181(3): 557-573.e18.

［11］Van Hove H, Martens L, Scheyltjens I, et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment ［J］. Nat Neurosci, 2019, 22(6): 1021-1035.

［12］Cui J, Xu H, Lehtinen MK. Macrophages on the margin: choroid plexus immune responses ［J］. Trends Neurosci, 2021, 44(11): 864-875.

［13］Mrdjen D, Pavlovic A, Hartmann FJ, et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease ［J］. Immunity, 2018, 48(2): 380-395.e6.

［14］Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease ［J］. Nat Rev Immunol, 2018, 18(4): 225-242.

［15］Silvin A, Qian J, Ginhoux F. Brain macrophage development, diversity and dysregulation in health and disease ［J］. Cell Mol Immunol, 2023, 20(11): 1277-1289.

［16］Fan F, Su B, Kolodychak A, et al. Hyaluronic acid hydrogels with phototunable supramolecular cross-linking for spatially controlled lymphatic tube formation ［J］. ACS Appl Mater Interfaces, 2023, 15(50): 58181-58195.

［17］Ajami B, Samusik N, Wieghofer P, et al. Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models ［J］. Nat Neurosci, 2018, 21(4): 541-551.

［18］Gerganova G, Riddell A, Miller AA. CNS border-associated macrophages in the homeostatic and ischaemic brain ［J］. Pharmacol Ther, 2022, 240: 108220.

［19］Jord?o MJC, Sankowski R, Brendecke SM, et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation ［J］. Science, 2019, 363(6425):eaat7554.

［20］Kim JS, Kolesnikov M, Peled-Hajaj S, et al. A binary cre transgenic approach dissects microglia and CNS border-associated macrophages ［J］. Immunity, 2021, 54(1): 176-190.e7.

［21］Dalmau Gasull A, Glavan M, Samawar SKR, et al. The niche matters: origin, function and fate of CNS-associated macrophages during health and disease ［J］. Acta Neuropathol, 2024, 147(1): 37.

［22］Gerganova G, Riddell A, Miller AA. CNS border-associated macrophages in the homeostatic and ischaemic brain ［J］. Pharmacol Ther, 2022, 240: 108220.

［23］Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo ［J］. Science, 2005, 308(5726): 1314-1318.

［24］Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration ［J］. Annu Rev Immunol, 2017, 35: 441-468.

［25］Russo MV, Latour LL, Mcgavern DB. Distinct myeloid cell subsets promote meningeal remodeling and vascular repair after mild traumatic brain injury ［J］. Nat Immunol, 2018, 19(5): 442-452.

［26］Goldmann T, Wieghofer P, Jord?o MJC, et al. Origin, fate and dynamics of macrophages at central nervous system interfaces ［J］. Nat Immunol, 2016, 17(7): 797-805.

［27］Carpenter SJ, Mccarthy LE, Borison HL. Electron microscopic study of the epiplexus (Kolmer) cells of the cat choroid plexus ［J］. Z Zellforsch Mikrosk Anat, 1970, 110(4): 471-486.

［28］Lu J, Kaur C, Ling EA. Uptake of tracer by the epiplexus cells via the choroid plexus epithelium following an intravenous or intraperitoneal injection of horseradish peroxidase in rats ［J］. J Anat, 1993, 183: 609-617.

［29］Nakada T, Kwee IL, Igarashi H, et al. Aquaporin-4 functionality and virchow-robin space water dynamics: physiological model for neurovascular coupling and glymphatic flow ［J］. Int J Mol Sci, 2017, 18(8):1798.

［30］Zou W, Pu T, Feng W, et al. Blocking meningeal lymphatic drainage aggravates Parkinson’s disease-like pathology in mice overexpressing mutated α-synuclein ［J］. Transl Neurodegener, 2019, 8: 7.

［31］Jais A, Solas M, Backes H, et al. Myeloicell-derived VEGF maintains brain glucose uptake and limits cognitive impairment in obesity ［J］. Cell, 2016, 165(4): 882-895

［32］Mendes NF, Velloso LA. Perivascular macrophages in high-fat diet-induced hypothalamic inflammation ［J］. J Neuroinflammation, 2022, 19(1): 136.

［33］Zeisel A, Mu?oz-Manchado AB, Codeluppi S, et al. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq ［J］. Science, 2015, 347(6226): 1138-1142.

［34］Azucenas CR, Ruwe TA, Bonamer JP, et al. Comparative analysis of the functional properties of human and mouse ferroportin ［J］. Am J Physiol Cell Physiol, 2023, 324(5): C1110-C1118.

［35］Wen W, Cheng J, Tang Y. Brain perivascular macrophages: current understanding and future prospects ［J］. Brain, 2024, 147(1): 39-55.

［36］He H, Mack JJ, Gü? E, et al. Perivascular macrophages limit permeability ［J］. Arterioscler Thromb Vasc Biol, 2016, 36(11): 2203-2212.

［37］Galanternik MV, Castranova D, Gore AV, et al. A novel perivascular cell population in the zebrafish brain ［J］. Elife, 2017, 6: e24369.

［38］Serrats J, Schiltz JC, García-Bueno B, et al. Dual roles for perivascular macrophages in immune-to-brain signaling ［J］. Neuron, 2010, 65(1): 94-106.

［39］Vasilache AM, Qian H, Blomqvist A. Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E2 signaling ［J］. Brain Behav Immun, 2015, 48: 31-41.

［40］Self WK, Holtzman DM. Emerging diagnostics and therapeutics for Alzheimer disease ［J］. Nat Med, 2023, 29(9): 2187-2199.

［41］Tian ChL, Cerebral amyloid angiopathy ［J］. Chinese Journal of Neurology, 2021, 54(5): 499-507. (in Chinaese)

田成林. 脑淀粉样血管病［J］. 中华神经科杂志, 2021, (5): 499-507.

［42］Hawkes CA, Mclaurin J. Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy ［J］. Proc Natl Acad Sci USA, 2009, 106(4): 1261-1266.

［43］Hu M, Li T, Ma X, et al. Macrophage lineage cellsderived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model ［J］. Nat Commun, 2023, 14(1): 3945.

［44］Mildner A, Schlevogt B, Kierdorf K, et al. Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer’s disease ［J］. J Neurosci, 2011, 31(31): 11159-11171.

［45］El Khoury J, Toft M, Hickman SE, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease ［J］. Nat Med, 2007, 13(4): 432-438.

［46］Taylor X, Clark IM, Fitzgerald GJ, et al. Amyloid-β (Aβ) immunotherapy induced microhemorrhages are associated with activated perivascular macrophages and peripheral monocyte recruitment in Alzheimer’s disease mice ［J］. Mol Neurodegener, 2023, 18(1): 59.

［47］Sankowski R, Ahmari J, Mezö C, et al. Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease ［J］. EMBO J, 2021, 40(23): e108605.

［48］GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019 ［J］. Lancet Neurol, 2021, 20(10): 795-820.

［49］Wang CY, Cao LM, Shi J, et al. A prospective cohort study on blood pressure control and risk of ischemic stroke in patients with hypertension ［J］. Zhonghua Yu Fang Yi Xue Za Zhi, 2020, 54(7): 737-741.

［50］Liu Y, Jacobowitz DM, Barone F, et al. Quantitation of perivascular monocytes and macrophages around cerebral blood vessels of hypertensive and aged rats ［J］. J Cereb Blood Flow Metab, 1994, 14(2): 348-352.

［51］Pedragosa J, Salas-Perdomo A, Gallizioli M, et al. CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage ［J］. Acta Neuropathol Commun, 2018, 6(1): 76.

［52］Zhou J, Tang PC, Qin L, et al. CXCR3-dependent accumulation and activation of perivascular macrophages is necessary for homeostatic arterial remodeling to hemodynamic stresses ［J］. J Exp Med, 2010, 207(9): 1951-1966.

［53］Faraco G, Sugiyama Y, Lane D, et al. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension ［J］. J Clin Invest, 2016, 126(12): 4674-4689.

［54］Pires PW, Girgla SS, Mcclain JL, et al. Improvement in middle cerebral artery structure and endothelial function in stroke-prone spontaneously hypertensive rats after macrophage depletion ［J］. Microcirculation, 2013, 20(7): 650-661.

［55］Bhargava P, Kim S, Reyes AA, et al. Imaging meningeal inflammation in CNS autoimmunity identifies a therapeutic role for BTK inhibition ［J］. Brain, 2021, 144(5): 1396-1408.

［56］Lucchinetti CF, Popescu BF, Bunyan RF, et al. Inflammatory cortical demyelination in early multiple sclerosis ［J］. N Engl J Med, 2011, 365(23): 2188-2197.

［57］Derk J, Jones HE, Como C, et al. Living on the edge of the CNS: meninges cell diversity in health and disease ［J］. Front Cell Neurosci, 2021, 15: 703944.

［58］Merlini A, Haberl M, Strauß J, et al. Distinct roles of the meningeal layers in CNS autoimmunity ［J］. Nat Neurosci, 2022, 25(7): 887-899.

［59］Chen QL, Ye HQ, Chen WW. The pathogenesis of iron and oxidative stress in multiple sclerosis and advances in MRI ［J］. Chinese Journal of Magnetic Resonance Imaging, 2021,12(1):89-92.(in Chinese)

陈骞蓝, 叶海琪, 陈唯唯. 铁及氧化应激在多发性硬化中的作用机制及其MRI研究进展［J］. 磁共振成像, 2021, 12(1): 89-92.

［60］Locatelli G, Theodorou D, Kendirli A, et al. Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model ［J］. Nat Neurosci, 2018, 21(9): 1196-1208.

［61］Ivan DC, Berve KC, Walthert S, et al. Insulin-like growth factor-1 receptor controls the function of CNS-resident macrophages and their contribution to neuroinflammation ［J］. Acta Neuropathol Commun, 2023, 11(1): 35.

［62］Schonhoff AM, Figge DA, Williams GP, et al. Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease ［J］. Nat Commun, 2023, 14(1): 3754.

［63］Ochocka N, Segit P, Walentynowicz KA, et al. Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages ［J］. Nat Commun, 2021, 12(1): 1151.

［64］Guilliams M, Thierry GR, Bonnardel J, et al. Establishment and maintenance of the macrophage niche ［J］. Immunity, 2020, 52(3): 434-451.

［65］Dani N, Herbst RH, Mccabe C, et al. A cellular and spatial map of the choroid plexus across brain ventricles and ages ［J］. Cell, 2021, 184(11): 3056-3074.e21.