Inflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation
Autor: | Mark L. Andermann, Arthur U. Sugden, Osama Alturkistani, Jin Cui, Morgan L. Shannon, Maria K. Lehtinen, Neil Dani, Mya D. Webb, Frederick B. Shipley |
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Rok vydání: | 2020 |
Předmět: |
Receptors
CCR2 Inflammation CCL2 Biology General Biochemistry Genetics and Molecular Biology Tight Junctions 03 medical and health sciences Imaging Three-Dimensional 0302 clinical medicine Cerebrospinal fluid Immune system medicine Animals Molecular Biology Chemokine CCL2 Cell Proliferation Cerebrospinal Fluid 030304 developmental biology 0303 health sciences Calcium-Binding Proteins Microfilament Proteins Embryogenesis Cell Biology Macrophage Activation Embryonic stem cell Up-Regulation Cell biology Mice Inbred C57BL Choroid Plexus Choroid plexus Inflammation Mediators medicine.symptom Neural development 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
Zdroj: | Developmental Cell. 55:617-628.e6 |
ISSN: | 1534-5807 |
Popis: | Summary The choroid plexus (ChP) regulates brain development by secreting instructive cues and providing a protective brain barrier. Here, we show that polyI:C-mediated maternal immune activation leads to an inflammatory response in the developing embryonic mouse brain that manifests as pro-inflammatory cerebrospinal fluid (CSF) and accumulation of ChP macrophages. Elevation of CSF-CCL2 was sufficient to drive ChP immune cell recruitment, activation, and proliferation. In addition, ChP macrophages abandoned their regular tiling pattern and relocated to the ChP-free margin where they breached the weakened epithelial barrier. We further found that these immune cells entered from the ChP into the brain via anatomically specialized “hotspots” at the distal tips of ChP villi. In vivo two-photon imaging demonstrated that surveillance behaviors in ChP macrophages had already emerged at this early stage of embryogenesis. Thus, the embryonic ChP forms a functional brain barrier that can mount an inflammatory response to external insults. |
Databáze: | OpenAIRE |
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