Neutrophils and viral-induced neurologic disease

Abstract

Infection of the central nervous system (CNS) by neurotropic viruses represents an increasing worldwide problem in terms of morbidity and mortality for people of all ages. Although unique structural features of the blood-brain-barrier (BBB) provide a physical and physiological barrier, a number of neurotropic viruses are able to enter the CNS resulting in a variety of pathological outcomes. Nonetheless, antigen-specific lymphocytes are ultimately able to accumulate within the CNS and contribute to defense by reducing or eliminating the invading viral pathogen. Alternatively, infiltration of activated cells of the immune system may be detrimental, as these cells can contribute to neuropathology that may result in long-term cellular damage or death. More recently, myeloid cells e.g. neutrophils have been implicated in contributing to both host defense and disease in response to viral infection of the CNS. This review highlights recent studies using coronavirus-induced neurologic disease as a model to determine how neutrophils affect effective control of viral replication as well as demyelination.

Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis

“…Here we identified perivascular neutrophil swarming in response to viral infection in the brain in regions of increased BBB permeability, potentially reflecting remodeling of the extravascular matrix (Kienle and Lä mmermann, 2016). Nevertheless, the impact of neutrophil migration appears to be context dependent, because an inducible astrocyte-specific CXCL1 transgenic model resulted in increased neutrophil migration, which was associated with demyelination, but not a breakdown of the BBB (Marro et al, 2016;Grist et al, 2018). In contrast, in a transgenic model of oligodendrocyte-specific CXCL1 constitutive expression, neutrophil infiltration into the brain was associated with disruption of the BBB and increased mortality without dysmyelination (Tani et al, 1996).…”

Modulation of Production of Th1/Th2 Cytokines in Peripheral Blood Mononuclear Cells and Neutrophils by Hepatitis C Virus Infection in Chronically Infected Patients

“…Functionally, neutrophils have been suggested to play a defensive role [2,3], as depletion of these immune cells leads to higher viral loads and subsequent death in a neurotropic JHM strain of mouse hepatitis viral infection [16] and an increase in viral multiplication and fatality in herpes simplex virus type-1 infection of the murine cornea [17]. In addition, neutrophils have been shown to contribute to the control of viral replication and the severity of neurological diseases [18]. Studies have shown intriguing cytokine effects on neutrophils: IFN-γ and TNF-α induce phagocytosis [19] and the intracellular killing of microorganisms [20].…”

COVID-19: What do we need to know about ICU delirium during the SARS-CoV-2 pandemic?

“…Infecting animals with coronavirus induced a significant neurological disorder that could be due to the presence of large amounts of the virus, particularly in the hippocampus [34,35]. This process, in turn, can induce an inflammatory brain response with uncontrolled activation of astrocytes (astrogliosis) and infiltration of neutrophils through an inflamed blood-brain barrier [36]. When these changes occur, brain neurons are damaged, including around the hippocampus, which may result in nerve cell degeneration with clinical dementia and cognitive impairment.…”