Impaired pathogen-induced autophagy and increased IL-1β and TNFα release in response to pathogenic triggers in secretory phase endometrial stromal cells of endometriosis patients

Research question: It is not clear whether innate immunity along with autophagy is altered in endometrial cells of patients with endometriosis. Design: This study evaluated the effects of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) stimulation on autophagy induction, pro-IL-1 beta expression, and secretion of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF alpha) in endometrial epithelial and/or stromal cells of patients with endometriosis (EE-endo, ES-endo, respectively), those of patients with hydrosalpinx (EE-hydro, ES-hydro, respectively) and those of healthy fertile women (EE-healthy, ES-healthy, respectively), with and without inhibition of autophagy by autophagy-related (ATG)13 gene small interfering RNA (siRNA). Results: Stimulation with either LPS or poly I:C triggered autophagy in EE/ES-healthy, whereas no significant induction was observed in either EE/ES-endo or EE/ES-hydro. In EE- and/or ES-healthy, IL-1 beta and/or TNF alpha secretion after stimulation with LPS or poly 1:0 was significantly higher in cells with ATG13 knockdown compared with those with siRNA control (P < 0.03), whereas no significant difference was observed in either EE/ES-endo or EE/ES-hydro. In the secretory phase ES-endo without autophagy inhibition, IL-1 beta and TNF alpha secretion were significantly higher compared with those of ES-healthy after stimulation with either LPS or poly I:C for 4 h (P < 0.001) and for 24 h (P < 0.01). Conclusion: Pathogen-induced autophagy was impaired in EE/ES-endo. Increased IL-1 beta and TNF alpha release in response to pathogenic triggers in the secretory phase ES-endo may result in the development of an inflammatory uterine microenvironment detrimental to successful embryo implantation.