Trained immunity modulates inflammation-induced fibrosis

Nat Commun. 2019 Dec 11;10(1):5670. doi: 10.1038/s41467-019-13636-x.


Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production, chromatin and metabolic modifications. Low-dose LPS training alleviates fibrosis and inflammation in a mouse model of systemic sclerosis (SSc), whereas BCG-training exacerbates disease in this model. Adoptive transfer of low-dose LPS-trained or BCG-trained macrophages also has beneficial or harmful effects, respectively. Furthermore, coculture with low-dose LPS trained macrophages reduces the fibro-inflammatory profile of fibroblasts from mice and patients with SSc, indicating that trained immunity might be a phenomenon that can be targeted to treat SSc and other autoimmune and inflammatory fibrotic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cytokines / genetics
  • Cytokines / immunology
  • Female
  • Fibrosis / genetics
  • Fibrosis / immunology*
  • Fibrosis / therapy
  • Humans
  • Immunity
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / therapy


  • Cytokines