The Role of the Immune System in Huntington’s Disease

Figure 2

Neuronal glia interactions in Huntington’s disease. Microglia/macrophages are essential for host defense and can trigger M1 or M2 responses. The dichotomous M1/M2 concept implies that M1 cells induce Th1 cells that produce proinflammatory cytokines like IFN-γ, while M2 cells induce Th2 cells that are associated with IL-4, IL-5, and IL-10 supporting anti-inflammatory effects or antibody production. Aggregates of mutant huntingtin (mhtt) are found in neurons, astrocytes, and microglia. With a decreased protective function due to fewer glutamate transporters, mhtt-containing astrocytes may contribute to excitotoxicity. Consequently, there is glutamate excitotoxicity and glutamate-induced apoptosis causing neurodegeneration. At the same time, mhtt enhances microglia function and leads to microglia activation. Migrating microglia secrete proinflammatory cytokines (e.g., TNFα) and nitric oxide thus contributing to neurotoxicity. Yet, simultaneously, phagocytic microglia may also produce neuroprotective factors.