Role of Dendritic Cells in Viral Brain Infections

Abstract

To gain access to the brain, a so-called immune-privileged organ due to its physical separation from the blood stream, pathogens and particularly viruses have been selected throughout evolution for their use of specific mechanisms. They can enter the central nervous system through direct infection of nerves or cerebral barriers or through cell-mediated transport. Indeed, peripheral lymphoid and myeloid immune cells can interact with the blood–brain and the blood–cerebrospinal fluid barriers and allow viral brain access using the “Trojan horse” mechanism. Among immune cells, at the frontier between innate and adaptive immune responses, dendritic cells (DCs) can be pathogen carriers, regulate or exacerbate antiviral responses and neuroinflammation, and therefore be involved in viral transmission and spread. In this review, we highlight an important contribution of DCs in the development and the consequences of viral brain infections.

Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity

“…DCs are natural sentinels of the brain participating in homeostasis surveillance but they can also potentiate neuroinflammation. For example, during CNS infection they potentiate T cell responses and release pro-inflammatory cytokines [ 14 ]. In brain disorders, number of DC in parenchyma and activation status have been found to be correlated with severity of the disease [ 54 ].…”

“…In brain disorders, number of DC in parenchyma and activation status have been found to be correlated with severity of the disease [ 54 ]. Under local or systemic inflammatory environment, chemotactic factors such as CCL2 [ 55 ] have been shown to favour DC recruitment and lead to their interaction with the BBB through expression of CAMs and their transmigration through the activation of specific adhesion and signalling mechanisms [ 14 ]. Interestingly, both the inflammatory environment of USUV- and WNV-infected BBB and the direct infection of DCs by both viruses led to the upregulation of CAMs, in particular DC-SIGN.…”

“…Indeed, immune cells play a central role in CNS surveillance and function. A tight balance between responses to infections and deleterious effects associated with neuroinflammation highlights ambiguous roles of immune cells during virus nervous spread [ 14 ]. During CNS inflammation, cytokines and chemokines will promote cellular neuroinvasion through multiple mechanisms, including upregulation of cell adhesion molecules (CAMs) on CNS barriers that will allow cell attachment and transmigration [ 15 ].…”

Experimental procedures for flow cytometry of wild type mouse brain: A systematic review

“…Given the importance of specific T cell memory subsets to overall immunity, future flow cytometry analysis of the brain may benefit from their inclusion. Surprisingly, a few reports listed migratory/residential DCs within WT/control mouse brains, albeit at extremely low levels (33,(52)(53)(54)(55), as microglia are thought to mediate brain immune surveillance (120)(121)(122).…”

Dendritic cell‐derived exosomal miR‐3064‐5p inhibits SIRT6/PCSK9 to protect the blood‐brain barrier after subarachnoid hemorrhage

“…[ 12 ] DCs have been shown to interact with the BBB to conveniently enter the central nervous system, supporting the regulation of antiviral and inflammatory responses by DCs. [ 13 ] Moreover, studies have shown that blood myeloid (mDCs) and plasmacytoid DCs (pDCs) in patients with SAH are reduced in number and impaired function. [ 14 ] After SAH, the IL‐23 level in the serum is increased, and IL‐23 is partially secreted by activated DCs.…”