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

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 l...

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Autores principales: Xu, Jia, He, Chao, Fang, Yi-Wei, Hu, Zhi-Yong, Peng, Mei-Lin, Chen, Yuan-Yao, Su, Yu-Fang, Liu, Chun-Yan, Zhang, Hui-Ping, Zhao, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10226493/
https://www.ncbi.nlm.nih.gov/pubmed/35915541
http://dx.doi.org/10.4103/aja202243
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author Xu, Jia
He, Chao
Fang, Yi-Wei
Hu, Zhi-Yong
Peng, Mei-Lin
Chen, Yuan-Yao
Su, Yu-Fang
Liu, Chun-Yan
Zhang, Hui-Ping
Zhao, Kai
author_facet Xu, Jia
He, Chao
Fang, Yi-Wei
Hu, Zhi-Yong
Peng, Mei-Lin
Chen, Yuan-Yao
Su, Yu-Fang
Liu, Chun-Yan
Zhang, Hui-Ping
Zhao, Kai
author_sort Xu, Jia
collection PubMed
description 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.
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spelling pubmed-102264932023-05-30 Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis Xu, Jia He, Chao Fang, Yi-Wei Hu, Zhi-Yong Peng, Mei-Lin Chen, Yuan-Yao Su, Yu-Fang Liu, Chun-Yan Zhang, Hui-Ping Zhao, Kai Asian J Androl Original Article 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. Wolters Kluwer - Medknow 2022-07-29 /pmc/articles/PMC10226493/ /pubmed/35915541 http://dx.doi.org/10.4103/aja202243 Text en Copyright: © The Author(s)(2022) https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Original Article
Xu, Jia
He, Chao
Fang, Yi-Wei
Hu, Zhi-Yong
Peng, Mei-Lin
Chen, Yuan-Yao
Su, Yu-Fang
Liu, Chun-Yan
Zhang, Hui-Ping
Zhao, Kai
Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis
title Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis
title_full Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis
title_fullStr Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis
title_full_unstemmed Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis
title_short Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis
title_sort testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by mir-155-5p in uropathogenic escherichia coli-induced orchitis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10226493/
https://www.ncbi.nlm.nih.gov/pubmed/35915541
http://dx.doi.org/10.4103/aja202243
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