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Immune Surveillance of the CNS following Infection and Injury
Open accessAbstract
The central nervous system (CNS) contains a sophisticated neural network that must be constantly surveyed in order to detect and mitigate a diverse array of challenges. The innate and adaptive immune systems actively participate in this surveillance, which is critical for the maintenance of CNS homeostasis and can facilitate the resolution of infections, degeneration, and tissue damage. Infections and sterile injuries represent two common challenges imposed on the CNS that require a prompt immune response. While the inducers of these two challenges differ in origin, the resultant responses orchestrated by the CNS share some overlapping features. Here, we review how the CNS immunologically discriminates between pathogens and sterile injuries, mobilizes an immune reaction, and, ultimately, regulates local and peripherally-derived immune cells to provide a supportive milieu for tissue repair.
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“In AD and CNS infections, pro- and anti-inflammatory signaling is primarily initiated by CNS resident immune cells, the astrocytes, and microglia (Di Benedetto et al., 2022; Russo and McGavern, 2015).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Russo and McGavern, 2015
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“A great deal is known about sterile injuries; they involve release of alarmins detected by damage-associated molecular pattern (DAMP) sensors such as Toll-like and purinergic receptors (131).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [131]
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BackgroundCD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology
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Neuroimmune System as a Driving Force for Plasticity Following CNS Injury
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The Molecular Pathophysiology of Concussion
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“IFNs are a family of proinflammatory and immunomodulatory cytokines with potent antiviral activities, the production of which can be attributed to a wide range of cell types, such as monocytes, macrophages, and microglia [11].”
BackgroundAutoimmunity, neuroinflammation, pathogen load: A decisive crosstalk in neuropsychiatric SLE
Jeltsch‐David, H., & Muller, S. (2016) · Journal of Autoimmunity · doi:10.1016/j.jaut.2016.04.005 · Cited by 40
Biomarkers and Associated Immune Mechanisms for Early Detection and Therapeutic Management of Sepsis
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“Microglial function during sepsis is a surprisingly understudied field, but new advances in understanding the robust response to infection in the brain are quickly growing (45,107).”
BackgroundPeng, P., Yu, H., Xing, C., Tao, B., Li, C. R., Huang, J., Ning, G., Zhang, B., & Feng, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112311 · Cited by 39
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“Peripheral immune cell trafficking into the brain is strictly controlled and limited by blood-brain barrier (BBB) (Russo and McGavern, 2015).”
InfluentialJiang, Y., Patel, C. D., Manivanh, R. V., North, B. J., Backes, I. M., Posner, D. A., Gilli, F., Pachner, A. R., Nguyen, L., & Leib, D. A. (2017) · mBio · doi:10.1128/mbio.00678-17 · Cited by 37
“Immune responses vary depending on the specific neural compartment, and immune privilege can be chronically altered by infection (3).”
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The NLRP3 Inflammasome in Neurodegenerative Disorders: Insights from Epileptic Models
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“…since it can facilitate the infiltration of immune and inflammatory cells into the brain, thereby promoting the activation of other immune cells, such as astrocytes or microglia, to release additional inflammatory mediators that exacerbate neuroinflammation leading to neurodegeneration [87].”
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“The atypical structure of the CNS parenchyma under homeostatic conditions may require distinct mechanisms of T cell interstitial motility from those utilized by T cells recruited to the CNS by inflammation and infection (112).”
BackgroundADP/P2Y1 aggravates inflammatory bowel disease through ERK5-mediated NLRP3 inflammasome activation
Zhang, C., Qin, J., Zhang, S., Zhang, N., Tan, B., Siwko, S. K., Zhang, Y., Wang, Q., Chen, J., Qian, M., et al. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0307-5 · Cited by 37
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Induction of Immune Surveillance of the Dysmorphogenic Lens
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“We also established an intracranial LPS-induced neuroinflammation mouse model, and designed experiments with a multimodal imaging approach using [18F]CB251 PET/MR and BLI technologies to understand the interaction between CNS and the peripheral immune system during neuroinflammation.”
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Human adipose-derived mesenchymal stem cells for acute and sub-acute TBI
Ruppert, K. A., Prabhakara, K. S., Furman, N. E. T., Udtha, S., Arceneaux, A. Q., Park, H., Dao, A., Cox, C. S., & Olson, S. D. (2020) · PLoS ONE · doi:10.1371/journal.pone.0233263 · Cited by 30
Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies
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Neuroimmunomodulatory properties of DPSCs in an in vitro model of Parkinson's disease
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“Next, they would get activated and initiate mechanisms leading to neuronal cell death (41,42).”
BackgroundFunctionally Competent, PD-1+ CD8+ Trm Cells Populate the Brain Following Local Antigen Encounter
Schøller, A. S., Nazerai, L., Christensen, J. P., & Thomsen, A. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.595707 · Cited by 26
“It is widely known that during the course of CNS inflammation, the number of CNS infiltrating leukocytes dramatically increases (2, 3).”
BackgroundNeuroinflammation in the Brain and Role of Intestinal Microbiota: An Overview of the Players
Cavaliere, G., & Traina, G. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2206148 · Cited by 29
“Such alterations permit microglial cells to move to the site of a lesion, where they can increase their phagocytic capacity to engulf and digest dead or damaged neurons [20].”
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“In fact, several recent observations suggest that induction of regeneration of normal CNS function may depend critically upon the co-initiation of an immune response (Gendelman, 2002; Nguyen et al., 2002; Pavlov and Tracey, 2015; Russo and McGavern, 2015).”
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Metadata
- Authors
- Russo, M. V., & McGavern, D. B.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- McGavern, Dorian B.
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 36
- Issue
- 10
- Pages
- 637-650
- ISSN
- 1471-4906 (ISSN-L)
- PMC
- PMC4592776
- OpenAlex
- W2116063788
- Cited by
- 191
- References
- 105
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 17 · 2023: 14 · 2022: 13 · 2021: 19 · 2020: 21 · 2019: 23 · 2018: 19 · 2017: 29 · 2016: 15
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- central nervous system infection, central nervous system injury, sterile injury, innate immunity, adaptive immunity, CNS homeostasis, pathogen discrimination, immune cell mobilization, tissue repair, neuroinflammation
- MeSH terms
- Animals, Central Nervous System, Central Nervous System Infections, Chemotaxis, Leukocyte, Humans, Immune System, Immunologic Surveillance, Wound Healing, Neuroimmunomodulation, Trauma, Nervous System, Receptors, Pattern Recognition, Host-Pathogen Interactions
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