TY - JOUR
T1 - Infections in the Developing Brain
T2 - The Role of the Neuro-Immune Axis
AU - Kim, John
AU - Erice, Clara
AU - Rohlwink, Ursula K.
AU - Tucker, Elizabeth W.
N1 - Funding Information:
ET is supported by the NIH NIAID K08AI139371 and the Hartwell Foundation−2018 Individual Biomedical Research Award. UR is supported by the Crick African Career Accelerated Award.
Publisher Copyright:
Copyright © 2022 Kim, Erice, Rohlwink and Tucker.
PY - 2022/2/17
Y1 - 2022/2/17
N2 - Central nervous system (CNS) infections occur more commonly in young children than in adults and pose unique challenges in the developing brain. This review builds on the distinct vulnerabilities in children's peripheral immune system (outlined in part 1 of this review series) and focuses on how the developing brain responds once a CNS infection occurs. Although the protective blood-brain barrier (BBB) matures early, pathogens enter the CNS and initiate a localized innate immune response with release of cytokines and chemokines to recruit peripheral immune cells that contribute to the inflammatory cascade. This immune response is initiated by the resident brain cells, microglia and astrocytes, which are not only integral to fighting the infection but also have important roles during normal brain development. Additionally, cytokines and other immune mediators such as matrix metalloproteinases from neurons, glia, and endothelial cells not only play a role in BBB permeability and peripheral cell recruitment, but also in brain maturation. Consequently, these immune modulators and the activation of microglia and astrocytes during infection adversely impact normal neurodevelopment. Perturbations to normal brain development manifest as neurodevelopmental and neurocognitive impairments common among children who survive CNS infections and are often permanent. In part 2 of the review series, we broadly summarize the unique challenges CNS infections create in a developing brain and explore the interaction of regulators of neurodevelopment and CNS immune response as part of the neuro-immune axis.
AB - Central nervous system (CNS) infections occur more commonly in young children than in adults and pose unique challenges in the developing brain. This review builds on the distinct vulnerabilities in children's peripheral immune system (outlined in part 1 of this review series) and focuses on how the developing brain responds once a CNS infection occurs. Although the protective blood-brain barrier (BBB) matures early, pathogens enter the CNS and initiate a localized innate immune response with release of cytokines and chemokines to recruit peripheral immune cells that contribute to the inflammatory cascade. This immune response is initiated by the resident brain cells, microglia and astrocytes, which are not only integral to fighting the infection but also have important roles during normal brain development. Additionally, cytokines and other immune mediators such as matrix metalloproteinases from neurons, glia, and endothelial cells not only play a role in BBB permeability and peripheral cell recruitment, but also in brain maturation. Consequently, these immune modulators and the activation of microglia and astrocytes during infection adversely impact normal neurodevelopment. Perturbations to normal brain development manifest as neurodevelopmental and neurocognitive impairments common among children who survive CNS infections and are often permanent. In part 2 of the review series, we broadly summarize the unique challenges CNS infections create in a developing brain and explore the interaction of regulators of neurodevelopment and CNS immune response as part of the neuro-immune axis.
KW - astrocyte
KW - central nervous system (CNS) infection
KW - development
KW - microglia
KW - neurological sequelae
KW - pediatrics
UR - http://www.scopus.com/inward/record.url?scp=85125705018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125705018&partnerID=8YFLogxK
U2 - 10.3389/fneur.2022.805786
DO - 10.3389/fneur.2022.805786
M3 - Review article
C2 - 35250814
AN - SCOPUS:85125705018
SN - 1664-2295
VL - 13
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 805786
ER -