Innate Immune Memory: Implications for Microglial Function and Neuroprogression.

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Immunostimulatory insults like stress and infection are linked to neuropsychiatric disorders with neuroprogression.
• Neuroprogression involves disruptions in neurogenesis, neuronal function, and survival due to inflammatory molecules.
• Peripheral innate immune cells exhibit 'innate immune memory,' retaining long-term inflammatory responses to insults.

Purpose of the Study:

• To hypothesize that microglia, the brain's innate immune cells, possess similar long-term memory capabilities.
• To explore the potential role of microglial memory in driving persistent neuroinflammation in neuropsychiatric illnesses.

Main Methods:

• Drawing on existing immunology literature regarding innate immune memory in peripheral cells.
• Extrapolating these concepts to microglia, the resident innate immune cells within the central nervous system.

Main Results:

• Microglia, like peripheral immune cells, may retain long-term memory of various insults, including stress and infection.
• This microglial memory can lead to sustained upregulation of proinflammatory and neurotoxic functions.

Conclusions:

• Persistent microglial activation, driven by innate immune memory, could be a key factor in the chronic inflammation characteristic of neuropsychiatric disorders.
• Microglial innate immune memory is proposed as a significant driver of neuroprogression in these conditions.