Understanding neuroinflammation through central nervous system infections

Abstract

Neuroinflammation is now recognized to compound many central nervous system (CNS) pathologies, from stroke to dementia. As immune responses evolved to handle infections, studying CNS infections can offer unique insights into the CNS immune response and address questions such as: What defenses and strategies do CNS parenchymal cells deploy in response to a dangerous pathogen? How do CNS cells interact with each other and infiltrating immune cells to control microbes? What pathways are beneficial for the host or for the pathogen? Here, we review recent studies that use CNS-tropic infections in combination with cutting-edge techniques to delve into the complex relationships between microbes, immune cells, and cells of the CNS.

Figure 1. Uninfected microglia recruit infiltrating immune cells and activate pathogen-specific T cells.

(a) In T. gondii-infected murine brains, microglia release IL-1α onto IL-1α receptors on the vascular endothelium, increasing T cell and myeloid-lineage cell recruitment into the CNS [5]. (b) Microglia acquire vesicular stomatitis virus (VSV) antigen from infected olfactory sensory neurons, which is then used to activate effector CD8⁺ T cells through T cell receptor– MHC-I interactions [6]. MHC, major histocompatibility complex.

Figure 2. Measles virus neurons transmit measles virus RNA to astrocytes through a non-canonical mechanism.

Measles virus (MV) infects murine neurons that ectopically express the human receptor hCD46. Viral riboproteins (RNP) can then spread to astrocytes that do not express hCD46. This spread requires direct contact with an infected neuron and glutamate/excitatory amino acid transporters. The MV genetic material can then spread from astrocyte-to-astrocyte through astrocyte-astrocyte membrane fusion events [25].