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.
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.
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 (LPS) or adoptive transfer of LPS-tolerized macrophages elicits a suppressor effect. LPS-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.
子宫内膜异位症是一种常见的慢性炎症性妇科疾病，其特征是存在异位子宫内膜组织，导致疼痛和不孕。巨噬细胞通过驱动慢性炎症和组织重塑，在病灶的建立和维持中起着核心作用。巨噬细胞可以在抗原刺激后被重新编程以获得类似记忆的特征，从而增强或抑制随后的免疫反应，这种现象称为“训练免疫”。在这里，卡介苗（BCG）训练增强了子宫内膜异位症小鼠模型中的病变生长，而用重复低剂量脂多糖（LPS）或过继转移 LPS 耐受的巨噬细胞进行耐受化则产生抑制作用。LPS 耐受的人巨噬细胞以白细胞介素 10（IL-10）依赖的方式减轻子宫内膜细胞的纤维炎症表型。严重革兰氏阴性感染史与降低不孕持续时间和减轻症状有关，与革兰氏阳性感染史的患者形成对比。因此，操纵固有免疫记忆可能在抑制过度炎症状态方面有效，为有前途的治疗方法开辟了道路。
