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Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates

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Title
Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates
Author(s)
Young-Chan Kim; Ji Hoon Ahn; Hokyung Jin; Myung Jin Yang; Seon Pyo Hong; Jin-Hui Yoon; Kim, Sang-Hoon; Gebre, Tirhas Niguse; Hyuek Jong Lee; Kim, You-Me; Gou Young Koh
Publication Date
2023-10
Journal
Science immunology, v.8, no.88
Publisher
American Association for the Advancement of Science
Abstract
High neonatal susceptibility to meningitis has been attributed to the anatomical barriers that act to protect the central nervous system (CNS) from infection being immature and not fully developed. However, the mechanisms by which pathogens breach CNS barriers are poorly understood. Using the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) to study virus propagation into the CNS during systemic infection, we demonstrate that mortality in neonatal, but not adult, mice is high after infection. Virus propagated extensively from the perivenous sinus region of the dura mater to the leptomeninges, choroid plexus, and cerebral cortex. Although the structural barrier of CNS border tissues is comparable between neonates and adults, immunofluorescence staining and single-cell RNA sequencing analyses revealed that the neonatal dural immune cells are immature and predominantly composed of CD206hi macrophages, with major histocompatibility complex class II (MHCII)hi macrophages being rare. In adults, however, perivenous sinus immune cells were enriched in MHCIIhi macrophages that are specialized for producing antiviral molecules and chemokines compared with CD206hi macrophages and protected the CNS against systemic virus invasion. Our findings clarify how systemic pathogens enter the CNS through its border tissues and how the immune barrier at the perivenous sinus region of the dura blocks pathogen access to the CNS.
URI
https://pr.ibs.re.kr/handle/8788114/14258
DOI
10.1126/sciimmunol.adg6155
ISSN
2470-9468
Appears in Collections:
Center for Vascular Research(혈관 연구단) > 1. Journal Papers (저널논문)
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