Macrophage Immune Memory Controls Endometriosis in Mice and Humans
Mohamed Jeljeli, Luiza Gama Coelho Riccio, Sandrine Chouzenoux, Fabiana Moresi, Laurie Toullec, Ludivine Doridot, Carole Nicco, Mathilde Bourdon, Louis Marcellin, Piétro Santulli, Maurício Simões Abrão, Charles Chapron, Frédéric Batteux
Abstract
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 (LPS low ) or adoptive transfer of LPS low -tolerized macrophages elicits a suppressor effect. LPS low -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.