Cell Reports · 2020 · 88 citations · 58 references
Life SciencesGynecologyImmunologyInflammationInnate ImmunityReproductive ImmunologyCytokine BiologyEndometriosisInflammatory ProcessesInflammatory SignalingMacrophage BiologyTrained ImmunityChronic Endometrial InflammationEndometrial Innate ImmunityEndometrial MacrophagesEndometrial Tissue RemodelingImmunization With Bacille Calmette-guérinInnate Immune FunctionLesion InitiationTrained Innate Immunity
Endometriosis is a chronic inflammatory gynecological disease marked by ectopic endometrial tissue that causes pain and infertility, with macrophages central to lesion establishment and maintenance through inflammation and tissue remodeling, and capable of acquiring trained‑immunity memory after antigenic challenge. BCG training increases lesion growth in a mouse model, whereas low‑dose LPS tolerization or transfer of LPS‑tolerized macrophages suppresses lesions, with LPS‑tolerized human macrophages reducing fibro‑inflammatory phenotypes via IL‑10, and a history of severe Gram‑negative infection correlating with shorter infertility duration and milder symptoms, suggesting that modulating innate immune memory could mitigate hyper‑inflammation and provide therapeutic avenues.
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.
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Johanneke Kleinnijenhuis, Jessica Quintin, Frank Preijers et al. · Proceedings of the National Academy of Sciences · 2012 · 1.7K citations · Full text