Microglia in Health and Diseases: Integrative Hubs of the Central Nervous System (CNS)
Open accessAbstract
Microglia are usually referred to as "the innate immune cells of the brain," "the resident macrophages of the central nervous system" (CNS), or "CNS parenchymal macrophages."These labels allude to their inherent immune function, related to their macrophage lineage.However, beyond their classic innate immune responses, microglia also play physiological roles crucial for proper brain development and maintenance of adult brain homeostasis.Microglia sense both external and local stimuli through a variety of surface receptors.Thus, they might serve as integrative hubs at the interface between the external environment and the CNS, able to decode, filter, and buffer cues from outside, with the aim of preserving and maintaining brain homeostasis.In this perspective, we will cast a critical look at how these multiple microglial functions are acquired and coordinated, and we will speculate on their impact on human brain physiology and pathology. MICROGLIA ACROSS THE LIFE SPANU nderstanding microglia requires becoming acquainted with their ontogeny, for which we rely on a concordant (where compared) set of observations in humans and mice.As with other tissue macrophages, such as those in skin and liver (Langerhans and Kupffer cells; Márquez-Ropero et al. 2020), microglia are not derived from bone marrow myeloid progenitors that
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Microglia constantly eliminate cell debris and dead cells through highly efficient phagocytosis.
“Microglia constantly eliminate cell debris and dead cells through highly efficient phagocytosis using specific recognition, engulfment, and degradation processes to maintain brain homeostasis in health and disease [310,325,326,327].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [310]
Cites
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · see citing works
Self-citationThe molecular hallmarks of epigenetic control
Allis, C. D., & Jenuwein, T. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.59 · Cited by 2,809 · see citing works
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · see citing works
Self-citationElmore, M. R. P., Najafi, A. R., Koike, M. A., Dagher, N. N., Spangenberg, E. E., Rice, R. A., Kitazawa, M., Matusow, B., Nguyen, H., West, B. L., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.040 · Cited by 1,968 · see citing works
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,788 · see citing works
Self-citationMicroglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis
Sierra, A., Encinas, J. M., Deudero, J. J. P., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., Tsirka, S. E., & Maletic-Savatic, M. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.014 · Cited by 1,622 · see citing works
Self-citationMicroglial interactions with synapses are modulated by visual experience
Tremblay, M.-È., Lowery, R. L., & Majewska, A. K. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000527 · Cited by 1,542 · see citing works
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
Masuda, T., Sankowski, R., Staszewski, O., Böttcher, C., Amann, L., Sagar, Scheiwe, C., Nessler, S., Kunz, P., van Loo, G., et al. (2019) · Nature · doi:10.1038/s41586-019-0924-x · Cited by 1,310 · see citing works
An environment-dependent transcriptional network specifies human microglia identity
Gosselin, D., Skola, D., Coufal, N. G., Holtman, I. R., Schlachetzki, J. C. M., Sajti, E., Jaeger, B. N., O’Connor, C., Fitzpatrick, C., Pasillas, M. P., et al. (2017) · Science · doi:10.1126/science.aal3222 · Cited by 1,220 · see citing works
Self-citationMicroglia development follows a stepwise program to regulate brain homeostasis
Matcovitch-Natan, O., Winter, D. R., Giladi, A., Vargas Aguilar, S., Spinrad, A., Sarrazin, S., Ben-Yehuda, H., David, E., Zelada González, F., Perrin, P., et al. (2016) · Science · doi:10.1126/science.aad8670 · Cited by 1,180 · see citing works
Van Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Pombo Antunes, A. R., De Prijck, S., Vandamme, N., De Schepper, S., Van Isterdael, G., Scott, C. L., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0393-4 · Cited by 1,160 · see citing works
Li, Q., Cheng, Z., Zhou, L., Darmanis, S., Neff, N. F., Okamoto, J., Gulati, G., Bennett, M. L., Sun, L. O., Clarke, L. E., et al. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.006 · Cited by 1,129 · see citing works
Innate immune memory in the brain shapes neurological disease hallmarks
Wendeln, A.-C., Degenhardt, K., Kaurani, L., Gertig, M., Ulas, T., Jain, G., Wagner, J., Häsler, L. M., Wild, K., Skodras, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0023-4 · Cited by 956 · see citing works
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease
Chen, W.-T., Lu, A., Craessaerts, K., Pavie, B., Sala Frigerio, C., Corthout, N., Qian, X., Laláková, J., Kühnemund, M., Voytyuk, I., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.038 · Cited by 949 · see citing works
Brain cell type–specific enhancer–promoter interactome maps and disease <b>-</b> risk association
Nott, A., Holtman, I. R., Coufal, N. G., Schlachetzki, J. C. M., Yu, M., Hu, R., Han, C. Z., Pena, M., Xiao, J., Wu, Y., et al. (2019) · Science · doi:10.1126/science.aay0793 · Cited by 823 · see citing works
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., & Pollard, J. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026317 · Cited by 649 · see citing works
Bruttger, J., Karram, K., Wörtge, S., Regen, T., Marini, F., Hoppmann, N., Klein, M., Blank, T., Yona, S., Wolf, Y., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.012 · Cited by 634 · see citing works
Greter, M., Lelios, I., Pelczar, P., Hoeffel, G., Price, J., Leboeuf, M., Kündig, T. M., Frei, K., Ginhoux, F., Merad, M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.11.001 · Cited by 630 · see citing works
A new fate mapping system reveals context-dependent random or clonal expansion of microglia
Tay, T. L., Mai, D., Dautzenberg, J., Fernández-Klett, F., Lin, G., Sagar, Datta, M., Drougard, A., Stempfl, T., Ardura-Fabregat, A., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4547 · Cited by 597 · see citing works
Microglia regulate central nervous system myelin growth and integrity
McNamara, N. B., Munro, D. A. D., Bestard-Cuche, N., Uyeda, A., Bogie, J. F. J., Hoffmann, A., Holloway, R. K., Molina-Gonzalez, I., Askew, K. E., Mitchell, S., et al. (2023) · Nature · doi:10.1038/s41586-022-05534-y · Cited by 507 · see citing works
Self-citationDistinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease
Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M., Möller, T., Biber, K., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02263-w · Cited by 441 · see citing works
Marsh, S. E., Walker, A. J., Kamath, T., Dissing-Olesen, L., Hammond, T. R., de Soysa, T. Y., Young, A. M. H., Murphy, S., Abdulraouf, A., Nadaf, N., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01022-8 · Cited by 432 · see citing works
Cronk, J. C., Filiano, A. J., Louveau, A., Marin, I., Marsh, R., Ji, E., Goldman, D. H., Smirnov, I., Geraci, N., Acton, S., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180247 · Cited by 412 · see citing works
Cholesterol and matrisome pathways dysregulated in astrocytes and microglia
TCW, J., Qian, L., Pipalia, N. H., Chao, M. J., Liang, S. A., Shi, Y., Jain, B. R., Bertelsen, S. E., Kapoor, M., Marcora, E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.017 · Cited by 411 · see citing works
Guerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurunlian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.579 · Cited by 374 · see citing works
Transcriptional signature in microglia associated with Aβ plaque phagocytosis
Grubman, A., Choo, X. Y., Chew, G., Ouyang, J. F., Sun, G., Croft, N. P., Rossello, F. J., Simmons, R., Buckberry, S., Landin, D. V., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23111-1 · Cited by 357 · see citing works
Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
Chen, Y., & Colonna, M. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202717 · Cited by 339 · see citing works
Central nervous system regeneration is driven by microglia necroptosis and repopulation
Lloyd, A. F., Davies, C. L., Holloway, R. K., Labrak, Y., Ireland, G., Carradori, D., Dillenburg, A., Borger, E., Soong, D., Richardson, J. C., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0418-z · Cited by 316 · see citing works
Self-citationLopes, K. D. P., Snijders, G. J. L., Humphrey, J., Allan, A., Sneeboer, M. A. M., Navarro, E., Schilder, B. M., Vialle, R. A., Parks, M., Missall, R., et al. (2022) · Nature Genetics · doi:10.1038/s41588-021-00976-y · Cited by 273 · see citing works
How microglia sense and regulate neuronal activity
Umpierre, A. D., & Wu, L. (2021) · Glia · doi:10.1002/glia.23961 · Cited by 237 · see citing works
Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology
Smith, A. M., Davey, K., Tsartsalis, S., Khozoie, C., Fancy, N., Tang, S. S., Liaptsi, E., Weinert, M., McGarry, A., Muirhead, R. C. J., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02372-6 · Cited by 209 · see citing works
<i>CSF1R</i> -related leukoencephalopathy: A major player in primary microgliopathies
Konno, T., Kasanuki, K., Ikeuchi, T., Dickson, D. W., & Wszolek, Z. K. (2018) · Neurology · doi:10.1212/wnl.0000000000006642 · Cited by 208 · see citing works
Claes, C., Danhash, E. P., Hasselmann, J., Chadarevian, J. P., Shabestari, S. K., England, W. E., Lim, T. E., Hidalgo, J. L. S., Spitale, R. C., Davtyan, H., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00473-0 · Cited by 197 · see citing works
Owen, D. R., Narayan, N., Wells, L., Healy, L., Smyth, E., Rabiner, E. A., Galloway, D., Williams, J. B., Lehr, J., Mandhair, H., et al. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17710182 · Cited by 194 · see citing works
Olson, M. C., Scott, E. W., Hack, A. A., Su, G. H., Tenen, D. G., Singh, H., & Simon, M. C. (1995) · Immunity · doi:10.1016/1074-7613(95)90060-8 · Cited by 191 · see citing works
A new genetic strategy for targeting microglia in development and disease
McKinsey, G. L., Lizama, C. O., Keown-Lang, A. E., Niu, A., Santander, N., Larpthaveesarp, A., Chee, E., Gonzalez, F. F., & Arnold, T. D. (2020) · eLife · doi:10.7554/elife.54590 · Cited by 176 · see citing works
A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages
Kim, J.-S., Kolesnikov, M., Peled-Hajaj, S., Scheyltjens, I., Xia, Y., Trzebanski, S., Haimon, Z., Shemer, A., Lubart, A., Van Hove, H., et al. (2021) · Immunity · doi:10.1016/j.immuni.2020.11.007 · Cited by 176 · see citing works
Directed evolution of adeno-associated virus for efficient gene delivery to microglia
Lin, R., Zhou, Y., Yan, T., Wang, R., Li, H., Wu, Z., Zhang, X., Zhou, X., Zhao, F., Zhang, L., et al. (2022) · Nature Methods · doi:10.1038/s41592-022-01547-7 · Cited by 171 · see citing works
Genetics of the human microglia regulome refines Alzheimer’s disease risk loci
Kosoy, R., Fullard, J. F., Zeng, B., Bendl, J., Dong, P., Rahman, S., Kleopoulos, S. P., Shao, Z., Girdhar, K., Humphrey, J., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01149-1 · Cited by 168 · see citing works
Absence of microglia promotes diverse pathologies and early lethality in Alzheimer’s disease mice
Kiani Shabestari, S., Morabito, S., Danhash, E. P., McQuade, A., Sanchez, J. R., Miyoshi, E., Chadarevian, J. P., Claes, C., Coburn, M. A., Hasselmann, J., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110961 · Cited by 167 · see citing works
Bassil, R., Shields, K., Granger, K., Zein, I., Ng, S., & Chih, B. (2021) · Nature Communications · doi:10.1038/s41467-021-25344-6 · Cited by 106 · see citing works
A comparative analysis of microglial inducible Cre lines
Faust, T. E., Feinberg, P. A., O’Connor, C., Kawaguchi, R., Chan, A., Strasburger, H., Frosch, M., Boyle, M. A., Masuda, T., Amann, L., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113031 · Cited by 103 · see citing works
Cantaut-Belarif, Y., Antri, M., Pizzarelli, R., Colasse, S., Vaccari, I., Soares, S., Renner, M., Dallel, R., Triller, A., & Bessis, A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201607048 · Cited by 56 · see citing works
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Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Bougnères, P., & Le Stunff, C. (2025) · Genes · doi:10.3390/genes16050590 · Cited by 11 · see citing works
- Authors
- Sierra, A., Miron, V. E., Paolicelli, R. C., & Ransohoff, R. M.
- Affiliations
- Ikerbasque (ES)
- University of Lausanne (CH)
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2024-03-04
- Volume
- 16
- Issue
- 8
- Pages
- a041366
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC11293550
- OpenAlex
- W4392380820
- Cited by
- 47
- References
- 44
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 7
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (197940)
- Eusko Jaurlaritza (PIBA 2020_1_0030)
- Ministerio de Ciencia e Innovación (MCIN/AEI/10, B-I00, .13039/501100011033, 10.13039, / AEI/10, MCIN/AEI/10.13039/501100011033,, 10.13039/501100011033/, 501100011033, PID2022, /AEI/10.13039/ 501100011033)
- Medical Research Council (MR/V031260/1, MRC/V031260/1)
- Agencia Estatal de Investigación (AEI//10.13039/501100011033/, 501100011033, 10.13039/501100011033, MCIN/AEI/10.13039/501 100 011 033, 13039, .13039/501100011033, 10.13039, AEI/10)
- H2020 European Research Council (804949)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, central nervous system, brain homeostasis, microglial receptors, innate immunity, macrophage lineage, brain development
- MeSH terms
- Animals, Brain, Central Nervous System, Homeostasis, Humans, Immunity, Innate, Microglia
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