Abstract
Innate immune memory was first described for monocytes and other myeloid cells. This memory is designated Immune Training, in which the host animals that had experienced pathogen infection earlier acquire improved resistance to a second infection. Innate immune memory is mediated by an epigenetic mechanism traced to transcriptional memory that is conserved throughout evolution and has been selected for the ability to mount an adaptive response to shifting environments. Accumulating evidence shows that not only peripheral myeloid cells but hematopoietic stem/progenitor cells (HSCs/HSPCs) can acquire epigenetic memory upon pathogen exposure. Systemic pathogen infection causes HSCs to exit from quiescence and facilitate myeloid-biased differentiation that leads to efficient host defense. This sequence of events is common in HSC memory generation, which is triggered by different stimuli. Recent studies show that not only pathogens but other stimuli such as metabolic stress can generate memory in HSCs. This review summarizes recent publications relevant to HSC memory. We discuss the current understanding of initial sensors, soluble mediators/cytokines involved in memory formation, including Type I and Type II interferons along with future implications.
Highlights
Epigenetic traits, such as histone modifications and certain gene expression programs are inherited through somatic cell divisions, allowing for the maintenance of phenotypic attributes across cell generations
The NLRP3 inflammasome pathway was involved in Western diet-induced trained immunity, in that the diet-induced effects were reversed in Ldlr-/-/Nlrp3-/- double knock-out mice, which exhibited a reduction in systemic inflammation, excessive hematopoiesis, and reprogramming of granulocyte monocyte progenitors (GMP)
Heme mediated immune training shared common features with bglucan driven training, such as upregulated glycolytic metabolism, and enrichment of AP-1 motif in accessible chromatin sites. These findings indicate that labile heme mediates training in LT-Hematopoietic Stem Cells (HSCs) facilitating long-term myelopoiesis with varying outcomes in host defense
Summary
Epigenetic traits, such as histone modifications and certain gene expression programs are inherited through somatic cell divisions, allowing for the maintenance of phenotypic attributes across cell generations. Consistent with this, open chromatin regions correlated with enhancer marks such as H3K3me and H3K27ac and are linked to genes involved in myeloid cell development and activity These observations indicate that LPS induced transcription factors set a new epigenetic mark in chromatin that leads to the establishment of innate immune memory. The NLRP3 inflammasome pathway was involved in Western diet-induced trained immunity, in that the diet-induced effects were reversed in Ldlr-/-/Nlrp3-/- double knock-out mice, which exhibited a reduction in systemic inflammation, excessive hematopoiesis, and reprogramming of GMPs. A prolonged Western diet is known to cause cholesterol overloading in HSCs, leading to an increase in the production of growth factors/cytokines, such as GM-CSF and IL-3. IFNs are another class of cytokines that take part in generating innate immune memory in HSCs and peripheral myeloid cells
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