Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis  

作　　者：Jia Xu Chao He Yi-Wei Fang Zhi-Yong Hu Mei-Lin Peng Yuan-Yao Chen Yu-Fang Su Chun-Yan Liu Hui-Ping Zhang Kai Zhao 

机构地区：[1]Institute of Reproductive Health,Center for Reproductive Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Asian Journal of Andrology》2023年第3期389-397,共9页亚洲男性学杂志（英文版）

基　　金：This work was funded by National Key R&D Program of China(2018YFC1004300 and 2018YFC1004304);National Natural Foundation of China(No.81871148 and No.818701539).

摘　　要：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.

关 键 词：male infertility miR-155-5p ORCHITIS testicular exosome testicular macrophage polarization 

分 类 号：R697[医药卫生—泌尿科学]