Endometriosis Patients Show an Increased M2 Response in the Peritoneal CD14(+low)/CD68(+low) Macrophage Subpopulation Coupled with an Increase in the T-helper 2 and T-regulatory Cells

Endometriosis is a chronic inflammatory disease associated with an impaired immune response at the site of lesion implantation. The ability of macrophages to respond to changes in their environment is critical for an effective immune response. However, the existing knowledge of the peritoneal immune cell populations, their activation state and contribution to the immunological changes that occur in endometriosis are still controversial and inconclusive. In this study, we have examined the relative abundance of peritoneal macrophage subtypes, in women with (n = 21) versus without (n = 18) endometriosis and disease-associated changes in the adaptive T cell response. Using flow cytometry, we showed that peritoneal fluid monocyte/macrophages are composed of two populations of cells that exhibit major differences in the levels of the CD14 and CD68 markers, which we classified as the CD14(+low)/CD68(+low) and CD14(+high)/CD68(+high) subpopulations. Moreover, endometriosis-associated changes in the macrophage subtypes occurred only in the CD14(+low)/CD68(+low) subpopulation. In this subpopulation, we found an increased macrophage type 2 response that was coupled with an increase in peritoneal T-helper 2 and T-regulatory cell populations in women with endometriosis, compared with controls. In summary, this study resolves conflicting data in the literature regarding changes in the peritoneal immune cell population in endometriosis and identifies CD14(+low)/CD68(+low) macrophages as the subpopulation that changes in response to the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s43032-020-00211-9) contains supplementary material, which is available to authorized users.