Mus musculus Raw sequence reads

Innate immune memory is an essential systematic reprogramming of innate immune cells, including macrophages , which occurs in response to stimuli and alters subsequent immune response. Innate immune memory is divided into two forms immune training and immune tolerance, which refers to enhanced or suppressed immune responses upon secondary stimulation respectively. In the periphery, immune training was demonstrated to enhance pathogen clearance. However, it has been well documented that innate immune training in monocyte cells contributes to the pathology of atherosclerosis. Microglia, the resident macrophages of CNS, are well known to be primed by active inflammatory processes to become permissive to amplified responses after a second inflammatory stimulus. Moreover, some studies have identified critical roles of microglial priming in CNS pathology, such as prison disease, aging, experimental autoimmune encephalomyelitis, and Wallerian degeneration. Intriguingly, a recent study showed that microglia developed the capacity for long-lasting immune memory by using a repeated injection of low-dose lipopolysaccharides (LPS) to mice, without LPS, into the brain, nor disturbing the BBB. Upon the second injection of LPS (2XLPS), brain-specific immune training was induced, which indicated that the pro-inflammatory cytokines in the brain were increased compared to that after 1XLPS. In contrast, peripheral immune tolerance occurred because brain cytokines were significantly decreased. Strikingly, immune training in microglia triggered by peripheral inflammation exacerbates neuroinflammation in Alzheimer's disease (AD). However, which specific signals contribute to the formation of innate immune training in microglia and how microglial immune training affects PD remain unknown.