Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Innate immunity in the central nervous system
Richard M. Ransohoff, Melissa A. Brown
Richard M. Ransohoff, Melissa A. Brown
Published April 2, 2012
Citation Information: J Clin Invest. 2012;122(4):1164-1171. https://doi.org/10.1172/JCI58644.
View: Text | PDF
Review Article has an altmetric score of 20

Innate immunity in the central nervous system

  • Text
  • PDF
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.

Authors

Richard M. Ransohoff, Melissa A. Brown

×

Figure 2

Innate recognition of infection or tissue injury.

Options: View larger image (or click on image) Download as PowerPoint
Innate recognition of infection or tissue injury.
Endogenous DAMPs such ...
Endogenous DAMPs such as HSP or exogenous bacterial PAMPs activate the innate immune cells of the CNS by engaging cell surface receptors such as TLRs. Ligation of TLRs initiates an intracellular signaling cascade that involves activation of NF-κB and MAPK activity, which leads to formation of transcription factor AP1. Together these components drive transcription of IL-1 family cytokine precursor proteins pro–IL-1β and pro–IL-18. NLRs are activated by cytosolic microbial products, changes in cytosolic pH, or potassium levels often associated with stimulation of the ligand-gated ion channel P2X7R by extracellular ATP. NLRs such as NALP3 are central constituents of inflammasomes, multiprotein complexes that mediate activation of caspase-1, which catalyzes cleavage and maturation of IL-1 family cytokines. Functional domains of inflammasome components include caspase activation and recruitment domains (CARDs), which are present in both caspase-1 and the adapter apoptosis-associated Speck-like protein containing CARD (ASC). PYD, pyrin domain.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Referenced in 1 policy sources
Posted by 1 X users
Referenced in 6 patents
Mentioned in 1 Google+ posts
1050 readers on Mendeley
1 readers on CiteULike
See more details