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Topic 1.5 Trained Innate Immunity

Epigenetic reprogramming is the key for innate immune memory

  • Chromatin go through changes
  • Then, immunity related gene expression increase
      1. Chromatin Status: promoter region of immunity related to immunity open
      1. Histone modification: H3K4me3, H3K27ac, H3K27me3
      1. DNA methylation: fDNA methylation level in promoter region decrease

Metabolic reprogramming

  • After training, metabolic pathway change from oxidative phosphorylation to glycolysis

Central and peripheral innate immune memory

Comparison Dimension Central Innate Immune Memory Peripheral Innate Immune Memory
Core Trained Cells Hematopoietic Stem Cells (HSCs) and myeloid progenitors (e.g., CMP, GMP) in the bone marrow Tissue-resident immune cells (e.g., tissue-resident macrophages, lung/spleen macrophages), NK cells, epidermal stem cells
Training Inducer Target Inducers (e.g., BCG, β-glucan) reach the bone marrow through systemic circulation Inducers act directly on immune cells in peripheral tissues (e.g., lungs, skin, spleen)
Memory Transmission Heritable to daughter cells: Trained HSCs/progenitors differentiate into "pre-trained" monocytes/neutrophils, which are transported to peripheral tissues via blood circulation Non-heritable to distant cells: Memory is limited to locally trained tissue-resident cells
Functional Scope Systemic protection: Enhances the responsiveness of immune cells throughout the body to infections Localized protection: Strengthens immune defense in specific tissues (e.g., lungs, skin)
Experimental Evidence Adoptive transfer of bone marrow cells from BCG-immunized mice (Kaufman et al., Cell 2018) LPS-induced lung tissue-resident innate immunity (Cell Reports 2024)
  • ==Central innate immune== memory relies on bone marrow hematopoietic stem cells (HSCs) and myeloid progenitors, achieves systemic protection through heritable epigenetic reprogramming (with trained traits passed to daughter cells),
  • while ==peripheral innate immune memory ==depends on tissue-resident cells (e.g., tissue-resident macrophages, NK cells), realizes localized defense via non-heritable local epigenetic/metabolic reprogramming (memory limited to local tissues) .