The Contribution of Microglia and Brain-Infiltrating Macrophages to the Pathogenesis of Neuroinflammatory and Neurodegenerative Diseases during TMEV Infection of the Central Nervous System

Abstract

The infection of the central nervous system (CNS) with neurotropic viruses induces neuroinflammation and is associated with the development of neuroinflammatory and neurodegenerative diseases, including multiple sclerosis and epilepsy. The activation of the innate and adaptive immune response, including microglial, macrophages, and T and B cells, while required for efficient viral control within the CNS, is also associated with neuropathology. Under healthy conditions, resident microglia play a pivotal role in maintaining CNS homeostasis. However, during pathological events, such as CNS viral infection, microglia become reactive, and immune cells from the periphery infiltrate into the brain, disrupting CNS homeostasis and contributing to disease development. Theiler’s murine encephalomyelitis virus (TMEV), a neurotropic picornavirus, is used in two distinct mouse models: TMEV-induced demyelination disease (TMEV-IDD) and TMEV-induced seizures, representing mouse models of multiple sclerosis and epilepsy, respectively. These murine models have contributed substantially to our understanding of the pathophysiology of MS and seizures/epilepsy following viral infection, serving as critical tools for identifying pharmacological targetable pathways to modulate disease development. This review aims to discuss the host–pathogen interaction during a neurotropic picornavirus infection and to shed light on our current understanding of the multifaceted roles played by microglia and macrophages in the context of these two complexes viral-induced disease.

Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging

“…The abnormal permeability of the blood-brain barrier (BBB) allows immune system cells to infiltrate CNS neuronal cells, initiating demyelination. Myelin antigen-specific T cells (CD8+ and CD4+ T cells) cross the BBB, contributing to events that result in the formation of demyelinating lesions [99][100][101]. The gut microbiota influences and modulates the balance between pro-and anti-inflammatory T cells in gutassociated lymphoid tissue [102,103].…”

Exploring the Role of Platelets in Virus-Induced Inflammatory Demyelinating Disease and Myocarditis

“…Viral tropism and the pathogenesis of distinct organs have been studied using animal models with various viruses with different tropisms. Theiler’s murine encephalomyelitis virus (TMEV) is a non-enveloped, positive-sense, single-stranded RNA virus that belongs to the family Picornaviridae and genus Cardiovirus , and is a natural pathogen of mice [ 4 , 5 , 6 ]. Following the viral inoculation, TMEV can infect both the CNS andheart, causing CNS and cardiac inflammation [ 7 ] ( Figure 1 ).…”