The choroid plexus—a multi-role player during infectious diseases of the CNS

Abstract

The choroid plexus (CP) is the source of cerebrospinal fluid (CSF) production and location of the blood-CSF barrier (BCSFB), which is constituted by the epithelial cells of the CP. Several infectious pathogens including viruses, bacteria, fungi and parasites cross the BCSFB to enter the central nervous system (CNS), ultimately leading to inflammatory infectious diseases like meningitis and meningoencephalitis. The CP responds to this challenge by the production of chemokines and cytokines as well as alterations of the barrier function of the BCSFB. During the course of CNS infectious disease host immune cells enter the CNS, eventually contributing to the cellular damage caused by the disease. Additional complications, which are in certain cases caused by choroid plexitis, can arise due to the response of the CP to the pathogens. In this review we will give an overview on the multiple functions of the CP during brain infections highlighting the CP as a multi-role player during infectious diseases of the CNS. In this context the importance of tools for investigation of these CP functions and a possible suitability of the CP as therapeutic target will be discussed.

A case of mistaken identity: CD11c‐eYFP+ cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells

“…These pathways provide potential routes of entry to the brain for airborne chemicals, allergens and a wide range of pathogens (Dando et al, 2014). CD11c-eYFP 1 cells were also seen within the choroid plexus which, although not part of the brain parenchyma, is an important site of entry for macromolecules, trafficking immune cells and pathogens into the cerebrospinal fluid and subarachnoid space (Schwerk et al, 2015). In addition, CD11c-eYFP 1 cells were found within the circumventricular organs, which possess a fenestrated vascular network and thus lack a blood-brain barrier (Morita et al, 2016).…”

Infectious immunity in the central nervous system and brain function

“…Bacteria, fungi, viruses and parasites may initially gain access to the CSF across vessels within the meninges and ventricular system, which are fenestrated and nonrestrictive 22 . In comparison, CNS parenchymal vessels have specializations that provide a barrier to blood-borne pathogens, cells and large molecules.…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…A number of pathogens, including Streptococcus suis, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, and Trypanosoma brucei, to just name a few, have been shown to use the choroidal epithelium as a CNS entry site (summarized in [131]). These pathogens may cross the epithelium directly via paracellular or transcellular routes or use Trojan horse approaches to breach the barrier [31].…”

“…The choroid plexus responds to these pathogens by eliciting a stereotype programmed innate inflammatory host response leading to an increased expression of cytokines and chemokines that trigger BCSFB breakdown and eventually to an increased CNS invasion of pathogenic inflammatory cells into the CNS. In this context, the direct response of the choroid plexuses to the infectious agents will in addition to CNS invasion of the pathogens contribute to the pathogenesis of these neuroinflammatory diseases [131].…”