Other diseases
Human and mouse macrophages trained by low-dose LPS attenuate the inflammatory phenotype of endometriotic cells via an IL-10-dependent pathway, and significantly upregulated H3K4me3 on the IL-10 promoter and altered inflammatory cytokine production have been observed simultaneously in endometriosis 78. In addition, evidence of macrophage memory has also been obtained with respect neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder 55. In a mouse model of Alzheimer’s pathology, LPS-induced immune training has been demonstrated to exacerbate cerebral β-amyloidosis, whereas this could be alleviated by immune tolerance, attributable to microglial (brain-resident macrophage) memory, along with altered inflammatory cytokine production and H3K4me1 and H3K27ac enrichment79. Furthermore, in respiratory diseases such as allergic asthma, allergen-triggered macrophages have been observed to acquire a TNF-dependent inflammatory memory and show an excessive mediator response upon stimulation, thereby resulting in a shift toward an M2-like macrophage phenotype and the production of diverse inflammatory cytokines. Conversely, TNF blockade or genetic ablation has been found to prevent the inflammatory imprinting of macrophages80. The concept of macrophage memory presents a new perspective for better understanding of disease pathology, and elucidating the precise underlying mechanisms may provide relevant insights for the development of novel therapeutic strategies.