【神経科学】マウスの神経疾患の進行に影響を及ぼす脳の免疫記憶

Immune responses in the body affect the severity of mice brain disorders later in life through immune memory, reports a paper published online this week in Nature.

The innate immune system can retain a ‘memory’ of infection that lasts for months, altering subsequent immune responses. Immune memory has two forms: training, in which responses are augmented to fight reinfection; and tolerance, in which continuous exposure suppresses responses. Although it has been established that inflammation in the body can prompt immune responses in the brain, it is unknown whether immune memory occurs in the brain’s innate immune cells - the microglia. The possibility of manipulating microglial responses is of great interest, as these cells affect conditions such as Alzheimer’s disease and stroke. In addition, these cells are extremely long lived, and therefore potentially long-lasting, if not permanent, modification might be possible.

Jonas Neher and colleagues injected the bacterial component lipopolysaccharide into the bodies of mice that model Alzheimer’s disease and show the characteristic build-up of the protein amyloid-beta in the mice brains. Amyloid plaques activate microglia, which are thought to ingest and dispose of the protein. With one injection of lipopolysaccharide, the microglia appeared to develop a training response. After six months, more amyloid-beta had accumulated than in the non-injected control mice. Four injections, however, led to immune tolerance, resulting in a diminished amyloid-beta load. Similarly, the authors found that tolerance reduced neuronal damage after stroke. Tapping into these processes may offer a new route to alleviate neurological diseases.