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

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

Return

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

Author: Jia XU ¹ ; Chao HE ¹ ; Yi-Wei FANG ¹ ; Zhi-Yong HU ¹ ; Mei-Lin PENG ¹ ; Yuan-Yao CHEN ¹ ; Yu-Fang SU ¹ ; Chun-Yan LIU ¹ ; Hui-Ping ZHANG ¹ ; Kai ZHAO ¹
Author Information

1. Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Publication Type:Journal Article
Keywords: male infertility; miR-155-5p; orchitis; testicular exosome; testicular macrophage polarization
MeSH: Humans; Male; Mice; Animals; Orchitis; Uropathogenic Escherichia coli/metabolism*; MicroRNAs/metabolism*; Exosomes/metabolism*; Macrophages/metabolism*; Phenotype; Infertility, Male/metabolism*
From: Asian Journal of Andrology 2023;25(3):389-397
CountryChina
Language:English
Abstract: 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.