Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Asian J Androl. 2023 May-Jun;25(3):389-397. doi: 10.4103/aja202243.
Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
男性生殖系统感染已知会影响睾丸的免疫稳态，导致男性不育。然而，这些变化的确切发病机制仍知之甚少。在局部微环境和受体细胞之间的通讯中，炎症微环境中释放的外泌体起着重要作用。在这里，我们旨在确定炎症性睾丸来源的外泌体（IT-exos）的免疫调节特性，并探讨其在睾丸炎中的潜在机制。使用尿路致病性大肠杆菌（UPEC）诱导的睾丸炎模型分离 IT-exos，并证实 IT-exos 在体外促进促炎 M1 激活，TNF-α（TNF-α）、白细胞介素 1β（IL-1β）和白细胞介素 6（IL-6）的表达增加。我们进一步使用小 RNA 测序分别鉴定正常和 UPEC 感染睾丸中外泌体和原发性睾丸巨噬细胞（TM）中的差异 miRNA 图谱，并鉴定出 IT-exos 和炎症性睾丸中的 TM 中富含 miR-155-5p。转染 miR-155-5p 模拟物的骨髓来源巨噬细胞（BMDMs）的进一步研究表明，巨噬细胞极化为促炎表型。此外，给予 IT-exos 的小鼠显示出 TM1 样巨噬细胞的显著激活；然而，沉默 miR-155-5p 的 IT-exos 显示出促炎反应的减少。总体而言，我们证明了 IT-exos 携带的 miR-155-5p 在 UPEC 诱导的睾丸炎中 TM1 的激活中起着重要作用。我们的研究为炎症相关男性不育的免疫机制提供了新的视角。
