1. Immunology and Inflammation

Toll-like receptors (TLRs) in the trained immunity era

  1. Lena Alexopoulou  Is a corresponding author
  2. Magali Irla  Is a corresponding author
  1. Aix Marseille University, CNRS UMR7280, INSERM U1104 Centre d'immunologie de Marseille-Luminy (CIML), France
https://doi.org/10.7554/eLife.106443
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  1. Lena Alexopoulou
  2. Magali Irla
(2025)
Toll-like receptors (TLRs) in the trained immunity era
eLife 14:e106443.
https://doi.org/10.7554/eLife.106443
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Toll-like receptor (TLR) microbial ligands and TLR-mediated immune responses.

TLRs expressed on the cell surface recognize microbial membrane components, while TLRs expressed intracellularly in endosomal compartments recognize nucleic acids. Upon ligand binding, TLRs form homodimers or heterodimers and recruit adaptor molecules, such as MyD88 (myeloid differentiation primary-response protein 88), TIRAP (TIR-associated protein), TRAM (TRIF-related adaptor molecule), and/or TRIF (TIR domain-containing adaptor protein inducing IFN-β). Each TLR recruits a specific combination of adaptor molecules to activate downstream signaling cascades that lead to the production of inflammatory cytokines and type I IFNs.

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Trained immunity, mediated by epigenetic reprogramming, confers enhanced protection against secondary infection.

A primary infection induces epigenetic reprogramming of activated genes in innate immune cells, enabling an amplified response to subsequent infections over time. This is characterized by a reduced DNA methylation status and the deposition of histone chromatin marks. These epigenetic changes persist partially after the primary stimulus ceases, facilitating rapid transcription of pro-inflammatory genes during re-infection. H3K4me, histone 3 lysine 4 methylation; H3K4me1, histone 3 lysine 4 mono-methylation; H3K27ac, histone 3 lysine 27 acetylation.

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  1. Lena Alexopoulou
  2. Magali Irla
(2025)
Toll-like receptors (TLRs) in the trained immunity era
eLife 14:e106443.
https://doi.org/10.7554/eLife.106443