Macrophage Immune Memory Controls Endometriosis in Mice and Humans

Cell Rep. 2020 Nov 3;33(5):108325. doi: 10.1016/j.celrep.2020.108325.


Endometriosis is a frequent, chronic, inflammatory gynecological disease characterized by the presence of ectopic endometrial tissue causing pain and infertility. Macrophages have a central role in lesion establishment and maintenance by driving chronic inflammation and tissue remodeling. Macrophages can be reprogrammed to acquire memory-like characteristics after antigenic challenge to reinforce or inhibit a subsequent immune response, a phenomenon termed "trained immunity." Here, whereas bacille Calmette-Guérin (BCG) training enhances the lesion growth in a mice model of endometriosis, tolerization with repeated low doses of lipopolysaccharide (LPSlow) or adoptive transfer of LPSlow-tolerized macrophages elicits a suppressor effect. LPSlow-tolerized human macrophages mitigate the fibro-inflammatory phenotype of endometriotic cells in an interleukin-10 (IL-10)-dependent manner. A history of severe Gram-negative infection is associated with reduced infertility duration and alleviated symptoms, in contrast to patients with Gram-positive infection history. Thus, the manipulation of innate immune memory may be effective in dampening hyper-inflammatory conditions, opening the way to promising therapeutic approaches.

Keywords: IL-10; LPS; bacterial infections; endometriosis; fibrosis; immunology; inflammation; macrophages; mice; trained immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Endometriosis / immunology*
  • Endometriosis / microbiology
  • Endometriosis / pathology*
  • Female
  • Gram-Negative Bacterial Infections / complications
  • Humans
  • Immune Tolerance
  • Immunologic Memory*
  • Lipopolysaccharides
  • Macrophages, Peritoneal / immunology*
  • Mice
  • Phenotype


  • Cytokines
  • Lipopolysaccharides