Role of Microglia in Herpesvirus-Related Neuroinflammation and Neurodegeneration

Abstract

Neuroinflammation is defined as an inflammatory state within the central nervous system (CNS). Microglia conprise the resident tissue macrophages of the neuronal tissue. Upon viral infection of the CNS, microglia become activated and start to produce inflammatory mediators important for clearance of the virus, but an excessive neuroinflammation can harm nearby neuronal cells. Herpesviruses express several molecular mechanisms, which can modulate apoptosis of infected neurons, astrocytes and microglia but also divert immune response initiated by the infected cells. In this review we also describe the link between virus-related neuroinflammation, and development of neurodegenerative diseases.

A Comprehensive Overview of Epidemiology, Pathogenesis and the Management of Herpes Labialis

“…Many investigations have supported the idea that the HSV 1 regularly reactivates in the trigeminal ganglia after events such as immunosuppression, peripheral infection, and even stress. An increasing body of research suggests that asymptomatic infections occur often, followed by latency in neurons, and such recurring “mild” HSV-1 infections in the brain are associated with persistent neuroinflammation [ 38 , 39 ]. Microglia play an important role in the immune response to neuronal infection in the brain.…”

“…Microglia play an important role in the immune response to neuronal infection in the brain. Microglial cells endure an abortive infection after HSV-1 infection, proceeded by a burst of pro-inflammatory cytokine and chemokine release, which activates other glial cells within the CNS and recruits immune cells including NK cells, DC cells, and T lymphocytes to the brain [ 38 , 39 , 40 ]. HSV-1-infected microglial cells have also been demonstrated to produce reactive oxygen species which are directly responsible for damage to neurons [ 38 , 39 , 40 ].…”

“…Microglial cells endure an abortive infection after HSV-1 infection, proceeded by a burst of pro-inflammatory cytokine and chemokine release, which activates other glial cells within the CNS and recruits immune cells including NK cells, DC cells, and T lymphocytes to the brain [ 38 , 39 , 40 ]. HSV-1-infected microglial cells have also been demonstrated to produce reactive oxygen species which are directly responsible for damage to neurons [ 38 , 39 , 40 ]. Furthermore, it has been demonstrated that microglia continued in an active state in the brain of HSV1-infected mice until thirty days after infection, despite the absence of active replication [ 38 , 39 , 40 ].…”

“…HSV-1-infected microglial cells have also been demonstrated to produce reactive oxygen species which are directly responsible for damage to neurons [ 38 , 39 , 40 ]. Furthermore, it has been demonstrated that microglia continued in an active state in the brain of HSV1-infected mice until thirty days after infection, despite the absence of active replication [ 38 , 39 , 40 ]. However, whether the microglia have any role in the reactivation of herpes labialis is not yet known.…”

Glial Cells and Itch: Possible Targets for Novel Antipruritic Therapies

“…70 Microglia, which function as first-line immune guardians of the CNS, are the central drivers of neuroinflammation. 70 Increasing evidence suggests that microglia are key regulators of CNS diseases, such as Alzheimer's disease, multiple sclerosis, depression, and chronic pain. 71−74 Some studies have preliminarily evaluated the role of microglia in itch, which has often been overlooked.…”