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Cited by 1,034Neuroinflammation and Neurodegeneration MechanismsImmune Response and InflammationMultiple Sclerosis Research Studies

Innate immunity in the central nervous system

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Ransohoff, Richard M., Brown, Melissa A.·2012·Journal of Clinical Investigation
DOI 10.1172/jci58644PMC PMC3314450
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Abstract

Immune responses in the CNS are common, despite its perception as a site of immune privilege.These responses can be mediated by resident microglia and astrocytes, which are innate immune cells without direct counterparts in the periphery.Furthermore, CNS immune reactions often take place in virtual isolation from the innate/adaptive immune interplay that characterizes peripheral immunity.However, microglia and astrocytes also engage in significant cross-talk with CNS-infiltrating T cells and other components of the innate immune system.Here we review the cellular and molecular basis of innate immunity in the CNS and discuss what is known about how outcomes of these interactions can lead to resolution of infection, neurodegeneration, or neural repair depending on the context. Immune privilege: CNS innate immune cells do not phone homeAn essential function of innate immunity is to provide the informational input for adaptive immunity.In peripheral organs, innate DCs detect the presence and nature of pathogens (viral, bacterial, or protozoal; intracellular or extracellular) and, through the release of selective mediators, educate T cells about the specifics of pathogen threat.Once the T cell has been informed (primed and polarized), it is directed to the site that harbors the pathogen (1-4).Here other resident or infiltrating innate cells decode the expressed array of T cell cytokines and, in a perfect immunological world, carry out the appropriate host attack on pathogen (Figure 1). Inflammation in the CNS: the role for DCsDCs play a critical role in initiating T cell responses by taking up protein antigens in tissues, processing them into small peptides and then displaying them on their surface physically associated with MHC class II molecules.DCs migrate through afferent lymphatics to draining lymph nodes and present antigen to naive or memory T cells.Importantly, there is no evidence that DCs with such capacities reside in the healthy CNS parenchyma, nor do CNS resident immune cells prime naive T cells (reviewed in ref. 5).Cells carrying DC surface markers (e.g., CD11b, CD11c) are readily detected in the meningeal coverings of the CNS and in the choroid plexus, the site of cerebrospinal fluid synthesis (6).Although cells with DC markers are abundant in the inflamed CNS parenchyma, they are primarily observed after blood-brain barrier (BBB) disruption, suggesting that many are peripherally derived while others represent resident microglia induced to express such markers by locally expressed cytokines (7-10).The lack of parenchymal DCs and the fact that no other parenchymal CNS cells fit the operational definition of a DC (antigen uptake, migration to draining lymph nodes, and presentation to naive T cells) constitute the cellular basis of CNS immune privilege.Immune privilege of the CNS, a hoary concept whose definition has become swollen and imprecise over more than six decades can be reduced to two observations: (a) immunogens such as xenografts, viruses, or bacterial lysates fail to elicit adaptive immune responses following non-traumatic micro-injection into the CNS parenchyma and (b) peripheral immunization with the same immunogen leads to a brisk immune response to the CNS depot of antigen.

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  • Maintenance of certain brain functions is dependent on T cell actions in the CNS.

    “maintenance of certain brain functions is dependent on T cell actions in the CNS (31, 32)”

    From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [31]

    The section “Interactions between innate immune cells and T cells in the CNS” discusses T-cell-mediated inflammation, host defense, and repair after injury, but does not say that maintaining brain functions depends on T-cell actions. Searches for normal brain function, cognition, learning, and neural repair found no passage establishing that dependency. (LLM, conf=0.72)

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Authors
Ransohoff, R. M., & Brown, M. A.
Affiliations
  • Cleveland Clinic (US)
  • Northwestern University (US)
Corresponding author
Ransohoff, Richard M.
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2012-04-02
Volume
122
Issue
4
Pages
1164-1171
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci58644
PMC
PMC3314450
OpenAlex
W1975110303
Cited by
1,034
References
24
Citations by year
2026: 57 · 2025: 60 · 2024: 55 · 2023: 57 · 2022: 72 · 2021: 75 · 2020: 77 · 2019: 80 · 2018: 86 · 2017: 88 · 2016: 68 · 2015: 70 · 2014: 92 · 2013: 77 · 2012: 18
FWCI
7.65
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Multiple Sclerosis Society
  • Cleveland Clinic
  • National Institutes of Health (R21NS78420)
  • Lerner Research Institute, Cleveland Clinic
  • National Institute of Neurological Disorders and Stroke (K24 NS51400, R21NS78420, R0NS132151, K24NS051400)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
innate immunity, central nervous system, microglia, astrocytes, immune privilege, dendritic cells, blood-brain barrier, neuroinflammation, neurodegeneration, neural repair, T cell response, innate-adaptive immune crosstalk, neuroprotection, infection resolution, choroid plexus, meninges
MeSH terms
Animals, Astrocytes, Blood-Brain Barrier, Brain Injuries, Central Nervous System, Central Nervous System Infections, Chemotaxis, Leukocyte, Dendritic Cells, Disease Models, Animal, Humans, Immunity, Innate, Inflammation, Mast Cells, Neutrophils, Receptors, Immunologic, T-Lymphocyte Subsets, Cytokines, Microglia, Models, Immunological, Toll-Like Receptors, Mice, Transendothelial and Transepithelial Migration, Inflammasomes

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