The Role of M1- and M2-Type Macrophages in Neurological and Infectious Diseases

Abstract

Macrophages have a critical role in the outcome of neurological diseases, including neurodegenerative, autoimmune, vascular and microbial diseases. Macrophage role ranges from beneficial to pathogenic depending upon genetics, other components of innate and adaptive immunity, lifestyle and macrophage targets: aggregated molecules or bacterial and viral pathogens. Macrophages are attracted by chemokines to migrate into the brain and remove or inactivate pathogenic molecules. In the patients with neurodegenerative diseases, macrophages target aggregated molecules, amyloid-β1–42 (Aβ) and P-tau in Alzheimer’s disease (AD), and superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS), but also have autoimmune targets. In AD and ALS patients, macrophages in the pro-resolution M1M2 state are adapted to brain clearance and homeostasis, whereas in the proinflammatory M1 state are modulate to an anti-viral and antibacterial role, which may be associated with collateral damage to tissues. In HIV-1 and CoV2 viral infections, macrophages in M1 state are anti-viral but also pathogenic through inflammatory damage to the heart and the brain. In neurodegenerative diseases, the natural substances polyunsaturated fatty acids (PUFA), vitamins B and D, energy molecules, and flavonoids have beneficial effects on macrophage transcriptome and functions for brain clearance, but the effects are complex and depend on many variables.