Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface

Shipley, Frederick B.; Dani, Neil; Xu, Huixin; Deister, Christopher A.; Cui, Jin; Head, Joshua P.; Sadegh, Cameron; Fame, Ryann M.; Shannon, Morgan L.; Flores, Vanessa I.; Kishkovich, Thomas P.; Jang, Emily; Klein, Eric M.; Goldey, Glenn J.; He, Kangmin; Zhang, Yong; Holtzman, Michael J.; Kirchhausen, Tomas; Wyart, Claire; Moore, Christopher I.; Andermann, Mark L.; Lehtinen, Maria K.

doi:10.1016/j.neuron.2020.08.024

Cited by 74 publications

(43 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to their prominent position at the CNS border regions, CAMs are important immunological gatekeepers of the CNS (Prinz et al , 2017 ; Jordao et al , 2019 ; Kierdorf et al , 2019 ; Brioschi et al , 2020 ). Particularly, the CP has been identified as crucial for the immunological milieu of the brain parenchyma and cerebrospinal fluid with implications for brain development and aging (Baruch et al , 2014 ; Cui et al , 2020 ; Shipley et al , 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease

et al. 2021

View full text Add to dashboard Cite

The immune cells of the central nervous system (CNS) comprise parenchymal microglia and at the CNS border regions meningeal, perivascular, and choroid plexus macrophages (collectively called CNS‐associated macrophages, CAMs). While previous work has shown that microglial properties depend on environmental signals from the commensal microbiota, the effects of microbiota on CAMs are unknown. By combining several microbiota manipulation approaches, genetic mouse models, and single‐cell RNA‐sequencing, we have characterized CNS myeloid cell composition and function. Under steady‐state conditions, the transcriptional profiles and numbers of choroid plexus macrophages were found to be tightly regulated by complex microbiota. In contrast, perivascular and meningeal macrophages were affected to a lesser extent. An acute perturbation through viral infection evoked an attenuated immune response of all CAMs in germ‐free mice. We further assessed CAMs in a more chronic pathological state in 5xFAD mice, a model for Alzheimer’s disease, and found enhanced amyloid beta uptake exclusively by perivascular macrophages in germ‐free 5xFAD mice. Our results aid the understanding of distinct microbiota–CNS macrophage interactions during homeostasis and disease, which could potentially be targeted therapeutically.

show abstract

Section: Discussionmentioning

confidence: 99%

Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Mouse strain used was C57BL/6. Pure CSF samples were collected from the cisterna magna [ 39 ]. Blood samples were collected from the retromandibular vein.…”

Section: Methodsmentioning

confidence: 99%

“…CSF was collected by puncture of the cisterna magna with a glass capillary [ 39 ] and flash-frozen for further analysis. Per condition, 3 µL of precleared CSF were extracted by brief sonication in 200 µL of the indicated extraction buffers.…”

Section: Methodsmentioning

confidence: 99%

Redox Metabolism Measurement in Mammalian Cells and Tissues by LC-MS

et al. 2021

View full text Add to dashboard Cite

Cellular redox state is highly dynamic and delicately balanced between constant production of reactive oxygen species (ROS), and neutralization by endogenous antioxidants, such as glutathione. Physiologic ROS levels can function as signal transduction messengers, while high levels of ROS can react with and damage various molecules eliciting cellular toxicity. The redox state is reflective of the cell’s metabolic status and can inform on regulated cell-state transitions or various pathologies including aging and cancer. Therefore, methods that enable reliable, quantitative readout of the cellular redox state are imperative for scientists from multiple fields. Liquid-chromatography mass-spectrometry (LC-MS) based methods to detect small molecules that reflect the redox balance in the cell such as glutathione, NADH, and NADPH, have been developed and applied successfully, but because redox metabolites are very labile, these methods are not easily standardized or consolidated. Here, we report a robust LC-MS method for the simultaneous detection of several redox-reactive metabolites that is compatible with parallel global metabolic profiling in mammalian cells. We performed a comprehensive comparison between three commercial hydrophilic interaction chromatography (HILIC) columns, and we describe the application of our method in mammalian cells and tissues. The presented method is easily applicable and will enable the study of ROS function and oxidative stress in mammalian cells by researchers from various fields.

show abstract

“…From there, at least Th17 cells expressing the chemokine receptor CCR6 were suggested to cross the BCSFB expressing the CCR6 ligand CCL20 in a CCR6/CCL20-dependent manner ( 107 ). Direct evidence for the migration of T cells from the ChP across the BCSFB in vivo awaits application of recently developed advanced imaging methodologies of the ChP ( 108 ). It has also been proposed that rather than crossing the BBB, immune cells exit the ChP stroma at the base of the ChP where it folds out from the ventricular wall.…”

Section: The Role Of the Individual Brain Barriers In Regulating Immu...mentioning

confidence: 99%

How Does the Immune System Enter the Brain?

Mapunda

Tibar²,

Regragui³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Multiple Sclerosis (MS) is considered the most frequent inflammatory demyelinating disease of the central nervous system (CNS). It occurs with a variable prevalence across the world. A rich armamentarium of disease modifying therapies selectively targeting specific actions of the immune system is available for the treatment of MS. Understanding how and where immune cells are primed, how they access the CNS in MS and how immunomodulatory treatments affect neuroinflammation requires a proper knowledge on the mechanisms regulating immune cell trafficking and the special anatomy of the CNS. The brain barriers divide the CNS into different compartments that differ with respect to their accessibility to cells of the innate and adaptive immune system. In steady state, the blood-brain barrier (BBB) limits immune cell trafficking to activated T cells, which can reach the cerebrospinal fluid (CSF) filled compartments to ensure CNS immune surveillance. In MS immune cells breach a second barrier, the glia limitans to reach the CNS parenchyma. Here we will summarize the role of the endothelial, epithelial and glial brain barriers in regulating immune cell entry into the CNS and which immunomodulatory treatments for MS target the brain barriers. Finally, we will explore current knowledge on genetic and environmental factors that may influence immune cell entry into the CNS during neuroinflammation in Africa.

show abstract

Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface

Cited by 74 publications

References 78 publications

Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease

Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease

Redox Metabolism Measurement in Mammalian Cells and Tissues by LC-MS

How Does the Immune System Enter the Brain?

Contact Info

Product

Resources

About