The choroid plexus synergizes with immune cells during neuroinflammation
Huixin Xu; Peter Lotfy; Sivan Gelb; Aja Pragana; Christine Hehnly; Lillian I.J. Byer; Frederick B. Shipley; Miriam E. Zawadzki; Jin Cui; Liwen Deng; Milo Taylor; Mya Webb; Hart G.W. Lidov; Mark L. Andermann; Isaac M. Chiu; Jose Ordovas-Montanes; Maria K. Lehtinen
The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation.
We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF. Bi-directional recruitment of monocytes from the periphery and, unexpectedly, macrophages from the CSF to the ChP helped eliminate neutrophils and repair the barrier. Transcriptomic analyses detailed the molecular steps accompanying this process and revealed that ChP epithelial cells transiently specialize to nurture immune cells, coordinating their recruitment, survival, and differentiation as well as regulation of the tight junctions that control the permeability of the ChP brain barrier.
Collectively, we provide a mechanistic understanding and a comprehensive roadmap of neuroinflammation at the ChP brain barrier.
Highlights
- The choroid plexus (ChP) is a hub of immune activity following acute brain inflammation
- Live imaging reveals immune cell recruitment to the ChP from the brain and periphery
- Specialized ChP epithelial cells coordinate stepwise responses to inflammation
- Macrophages participate in ChP barrier repair
Link | PDF (Cell) [Open Access]
Huixin Xu; Peter Lotfy; Sivan Gelb; Aja Pragana; Christine Hehnly; Lillian I.J. Byer; Frederick B. Shipley; Miriam E. Zawadzki; Jin Cui; Liwen Deng; Milo Taylor; Mya Webb; Hart G.W. Lidov; Mark L. Andermann; Isaac M. Chiu; Jose Ordovas-Montanes; Maria K. Lehtinen
The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation.
We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF. Bi-directional recruitment of monocytes from the periphery and, unexpectedly, macrophages from the CSF to the ChP helped eliminate neutrophils and repair the barrier. Transcriptomic analyses detailed the molecular steps accompanying this process and revealed that ChP epithelial cells transiently specialize to nurture immune cells, coordinating their recruitment, survival, and differentiation as well as regulation of the tight junctions that control the permeability of the ChP brain barrier.
Collectively, we provide a mechanistic understanding and a comprehensive roadmap of neuroinflammation at the ChP brain barrier.
Highlights
- The choroid plexus (ChP) is a hub of immune activity following acute brain inflammation
- Live imaging reveals immune cell recruitment to the ChP from the brain and periphery
- Specialized ChP epithelial cells coordinate stepwise responses to inflammation
- Macrophages participate in ChP barrier repair
Link | PDF (Cell) [Open Access]