Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease

Figure 2

A model of NK cell involvement in Alzheimer’s disease. Injury or infection can lead to the accumulation of Aβ peptides in the brain (1) and stimulates microglia and astrocytes (2). Accumulation of Aβ forming plaques induces the activation of complement system. C1q secreted by neurons can bind Aβ and activates C1q receptor (C1qR) on microglia promoting phagocytosis of Aβ. In addition, activated microglia secretes the proinflammatory cytokines IL-1β and IL-18.Astrocytes stimulated by inflammatory signals secrete C3 that is cleaved into C3b and C3a. C3a mediates recruitment of immune cells. This inflammatory environment can support trafficking of peripheral NK cells into the brain (3). NK cells are activated by microglia secreted cytokines and produce IFN-γ and TNF-α (4). Complement activation and proinflammatory cytokines can lead to neuronal damage and death (5).