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 (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.
Highlights
Endometriosis is a chronic, estrogen-dependent, inflammatory gynecological disease that affects about 5%–15% of women of reproductive age (Chapron et al, 2019)
In Vivo Immune Training Modulates Macrophages’ Phenotype and Cytokine Production We first analyzed the expression of surface molecules on peritoneal macrophages to better characterize the phenotypic changes upon in vivo immune training with LPSlow or bacille Calmette-Guerin (BCG) (Figure 1A)
Inflammatory stimulation of macrophages from PBS mice increased the release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), and IL10 when compared with basal cytokine production in nonstimulated macrophages
Summary
Endometriosis is a chronic, estrogen-dependent, inflammatory gynecological disease that affects about 5%–15% of women of reproductive age (Chapron et al, 2019). Menstrual regurgitation occurs in most women, and only 5%–15% suffer from endometriosis, indicating that additional factors favor the development of the disease. Molecular factors, such as inflammation, altered steroid biosynthesis and receptor response, and increased invasiveness, are involved in endometriosis development. Numerous studies have emphasized the role of chronic inflammation and aberrant immune response as major mechanisms for endometriosis development (Riccio et al, 2018) Abnormalities of both innate and adaptive immune responses, such as decreased T cell cytotoxicity, polyclonal activation of B cells, and altered activation of peritoneal macrophages with modifications in inflammatory mediators (Riccio et al, 2018) have been reported
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
