Macrophage Immune Memory Controls Endometriosis in Mice and Humans
Mohamed Jeljeli,
Luiza G.C. Riccio,
Sandrine Chouzenoux,
Fabiana Moresi,
Laurie Toullec,
Ludivine Doridot,
Carole Nicco,
Mathilde Bourdon,
Louis Marcellin,
Pietro Santulli,
Mauricio S. Abrão,
Charles Chapron,
Frédéric Batteux
Affiliations
Mohamed Jeljeli
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France; Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Service d’immunologie biologique, 75014 Paris, France
Luiza G.C. Riccio
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France; Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina FMUSP, Universidade de São Paulo, 01246903 São Paulo, Brasil
Sandrine Chouzenoux
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France
Fabiana Moresi
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France
Laurie Toullec
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France
Ludivine Doridot
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France
Carole Nicco
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France
Mathilde Bourdon
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France; Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction, 75014 Paris, France
Louis Marcellin
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France; Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction, 75014 Paris, France
Pietro Santulli
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France; Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction, 75014 Paris, France
Mauricio S. Abrão
Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina FMUSP, Universidade de São Paulo, 01246903 São Paulo, Brasil
Charles Chapron
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France; Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction, 75014 Paris, France
Frédéric Batteux
Département 3I, Infection, Immunité et Inflammation, Institut Cochin, INSERM U1016, Université de Paris, 75014 Paris, France; Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Service d’immunologie biologique, 75014 Paris, France; Corresponding author
Summary: 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.
