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Modulation of myelopoiesis progenitors is an integral component of trained immunity.

Cell 172, 147-161.e12 (2018)
Publishers Version Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
as soon as is submitted to ZB.
Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of beta-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1 beta and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gm-csf ; Cholesterol Biosynthesis ; Glycolysis ; Inflammation ; Innate Immune Memory ; Interleukin-1β ; Myelopoiesis ; Myelosuppression ; Trained Innate Immunity ; β-glucan; Hematopoietic Stem-cells; High-throughput; Self-renewal; Mass-spectrometry; Lineage Commitment; Global Analysis; Hypoxic Niche; Proliferation; Dormancy; Mice
Reviewing status
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)