Cited by 843Neuroinflammation and Neurodegeneration MechanismsInflammasome and immune disordersTraumatic Brain Injury and Neurovascular Disturbances

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Regulation of innate immune responses in the brain

Rivest, Serge·2009·Nature Reviews Immunology

DOI 10.1038/nri2565

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Abstract

Microglial cells are the main innate immune cells of the complex cellular structure of the brain. These cells respond quickly to pathogens and injury, accumulate in regions of degeneration and produce a wide variety of pro-inflammatory molecules. These observations have resulted in active debate regarding the exact role of microglial cells in the brain and whether they have beneficial or detrimental functions. Careful targeting of these cells could have therapeutic benefits for several types of trauma and disease specific to the central nervous system. This Review discusses the molecular details underlying the innate immune response in the brain during infection, injury and disease.

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Quan, N., Whiteside, M. B., Kim, L., & Herkenham, M. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10985 · Cited by 159
TLR-4 deficiency protects against focal cerebral ischemia and axotomy-induced neurodegeneration
Kılıç, Ü., Kılıç, E., Matter, C. M., Bassetti, C. L., & Hermann, D. M. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.03.002 · Cited by 159
Cooperation between toll‐like receptor 2 and 4 in the brain of mice challenged with cell wall components derived from gram‐negative and gram‐positive bacteria
Laflamme, N., Echchannaoui, H., Landmann, R. M., & Rivest, S. (2003) · European Journal of Immunology · doi:10.1002/eji.200323821 · Cited by 158
Self-citation
Regulation of the Gene Encoding Tumor Necrosis Factor Alpha (TNF-α) in the Rat Brain and Pituitary in Response to Different Models of Systemic Immune Challenge
Nadeau, S., & Rivest, S. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199901000-00008 · Cited by 142
Self-citation
Bone-marrow-derived microglia: myth or reality?
Soulet, D., & Rivest, S. (2008) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2008.04.002 · Cited by 139
Self-citation
Live imaging of Toll-like receptor 2 response in cerebral ischaemia reveals a role of olfactory bulb microglia as modulators of inflammation
Lalancette–Hébert, M., Phaneuf, D., Soucy, G., Weng, Y.-C., & Križ, J. (2009) · Brain · doi:10.1093/brain/awn345 · Cited by 138
G protein‐coupled receptor 84, a microglia‐associated protein expressed in neuroinflammatory conditions
Bouchard, C., Pagé, J., Bédard, A., Tremblay, P., & Vallières, L. (2007) · Glia · doi:10.1002/glia.20506 · Cited by 132
Innate immunity triggers oligodendrocyte progenitor reactivity and confines damages to brain injuries
Glezer, I., Lapointe, A., & Rivest, S. (2006) · The FASEB Journal · doi:10.1096/fj.05-5234fje · Cited by 131
Self-citation
Innate Immunity to Pneumococcal Infection of the Central Nervous System Depends on Toll‐Like Receptor (TLR) 2 and TLR4
Klein, M., Obermaier, B., Angele, B., Pfister, H., Wagner, H., Koedel, U., & Kirschning, C. J. (2008) · The Journal of Infectious Diseases · doi:10.1086/591626 · Cited by 130
Tumor Necrosis Factor α But Not Interleukin 1β Mediates Neuroprotection in Response to Acute Nitric Oxide Excitotoxicity
Turrin, N. P., & Rivest, S. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4032-05.2006 · Cited by 129
Self-citation
Increased Glioma Growth in Mice Depleted of Macrophages
Galarneau, H., de Villeneuve, J. P., Gowing, G., Julien, J., & Vallières, L. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0177 · Cited by 113
The role of macrophages in optic nerve regeneration
Cui, Q., Yin, Y., & Benowitz, L. I. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.07.036 · Cited by 106
Drug Insight: selective agonists and antagonists of the glucocorticoid receptor
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Endotoxemia prevents the cerebral inflammatory wave induced by intraparenchymal lipopolysaccharide injection: role of glucocorticoids and CD14
Nadeau, S., & Rivest, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.6.3370 · Cited by 94
Self-citation
Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system
Soulet, D., & Rivest, S. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200301097 · Cited by 93
Self-citation
Glucocorticoids: Protectors of the Brain during Innate Immune Responses
Glezer, I., & Rivest, S. (2004) · The Neuroscientist · doi:10.1177/1073858404263494 · Cited by 79
Self-citation
Endogenous signals initiating inflammation in the injured nervous system
Pineau, I., & Lacroix, S. (2008) · Glia · doi:10.1002/glia.20763 · Cited by 78
Delayed but Not Early Glucocorticoid Treatment Protects the Host during Experimental Herpes Simplex Virus Encephalitis in Mice
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Self-citation
Toll-like receptor 4 restricts retinal progenitor cell proliferation
Shechter, R., Ronen, A., Rolls, A., London, A., Bakalash, S., Young, M. J., & Schwartz, M. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200804010 · Cited by 77
Mouse model for ablation of proliferating microgliain acute CNS injuries
Gowing, G., Vallières, L., & Julien, J. (2005) · Glia · doi:10.1002/glia.20288 · Cited by 71
A 20-Year Overview
Bentovim, A. (2001) · IMPERIAL COLLEGE PRESS eBooks · doi:10.1142/9781848161528_0001 · Cited by 50
Intranasal herpes simplex virus type 2 inoculation causes a profound thymidine kinase dependent cerebral inflammatory response in the mouse hindbrain
Boivin, G., Coulombe, Z., & Rivest, S. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02057.x · Cited by 49
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Modulation of the Innate Immune Response by NMDA Receptors Has Neuropathological Consequences
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Genes Involved in the Balance between Neuronal Survival and Death during Inflammation
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Toll-like receptor-2 deficiency is associated with enhanced brain TNF gene expression during pneumococcal meningitis
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Cannabinoids in Microglia: A New Trick for Immune Surveillance and Neuroprotection
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CD14 receptor polymorphism and Alzheimer's disease risk
Combarros, O., Infante, J., Rodríguez‐Rodríguez, E., Llorca, J., Peña, N., Fernández‐Viadero, C., & Berciano, J. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.01.082 · Cited by 22
NLRs and the dangers of pollution and aging
Willingham, S. B., & Ting, J. P. ‐. (2008) · Nature Immunology · doi:10.1038/ni0808-831 · Cited by 17
Evidence for deficiencies in intracerebral cytokine production, adhesion molecule induction, and T cell recruitment in herpes simplex virus type-2 infected mice
Lewandowski, G. A., & Hobbs, M. V. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00159-8 · Cited by 15
Altered immune response to CNS viral infection in mice with a conditional knock‐down of macrophage‐lineage cells
Carmen, J., Gowing, G., Julien, J., & Kerr, D. A. (2006) · Glia · doi:10.1002/glia.20359 · Cited by 15

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Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
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An environment-dependent transcriptional network specifies human microglia identity
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Emerging targets in neuroinflammation-driven chronic pain
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Authors: Rivest, S.
Affiliations: Centre hospitalier universitaire de Québec (CA)
Corresponding author: Rivest, Serge
ORCID: Rivest, Serge
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2009-06
Volume: 9
Issue: 6
Pages: 429-439
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri2565
OpenAlex: W2145938600
Cited by: 843
References: 115
Citations by year: 2026: 17 · 2025: 24 · 2024: 25 · 2023: 33 · 2022: 47 · 2021: 42 · 2020: 40 · 2019: 43 · 2018: 48 · 2017: 52 · 2016: 54 · 2015: 79 · 2014: 86 · 2013: 69 · 2012: 69
FWCI: 4.71
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Canada Research Chairs
Canadian Institutes of Health Research
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: microglia, innate immunity, neuroinflammation, microglial activation, neuroprotection, neurodegeneration, Alzheimer's disease, infection, brain injury, proinflammatory molecules
MeSH terms: Alzheimer Disease, Amyloid, Animals, Brain, Encephalitis, Glucocorticoids, Humans, Immunity, Innate, Lipopolysaccharides, Oligodendroglia, Wounds and Injuries, Microglia, Toll-Like Receptors

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Regulation of innate immune responses in the brain

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