Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.
Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.
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DOI：
10.4103/aja202243
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发表时间：
2023-05
影响因子：
2.9
通讯作者：
Zhao K
中科院分区：
文献类型：
--
作者：
Xu J;He C;Fang YW;Hu ZY;Peng ML;Chen YY;Su YF;Liu CY;Zhang HP;Zhao K
已知男性生殖道感染会影响睾丸的免疫稳态，导致男性不育。然而，这些变化的具体发病机制仍然知之甚少。在炎症微环境中释放的外泌体在局部微环境和受体细胞之间的通信中是重要的。在这里，我们的目的是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在体外促进促炎性M1活化，增加肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1β）和白细胞介素-6（IL-6）的表达。我们进一步使用小RNA测序来分别鉴定来自正常和UPEC感染的睾丸的外泌体和初级睾丸巨噬细胞（TM）中的差异miRNA谱，并鉴定出miR-155- 5 p高度富集于炎性睾丸的IT-exos和TM中。对转染miR-155- 5 p模拟物的骨髓源性巨噬细胞（BMDM）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TM 1样巨噬细胞的显著活化;然而，沉默miR-155- 5 p的IT-exos显示出促炎反应的减少。总之，我们证明了由IT-exos递送的miR-155- 5 p在UPEC诱导的睾丸炎中激活TM 1中起重要作用。我们的研究为炎症相关的男性不育的免疫学机制提供了新的视角。
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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DOI：
10.1084/jem.20140654
发表时间：
2015-09-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baig MS;Zaichick SV;Mao M;de Abreu AL;Bakhshi FR;Hart PC;Saqib U;Deng J;Chatterjee S;Block ML;Vogel SM;Malik AB;Consolaro ME;Christman JW;Minshall RD;Gantner BN;Bonini MG
通讯作者：
Bonini MG
DOI：
10.1164/rccm.201701-0170oc
发表时间：
2017-11-15
影响因子：
24.7
作者：
Morrison, Thomas J.;Jackson, Megan V.;Krasnodembskaya, Anna D.
通讯作者：
Krasnodembskaya, Anna D.
影响因子：
1.2
作者：
Martin, Elodie;El-Behi, Mohamed;Delarasse, Cecile
通讯作者：
Delarasse, Cecile
传染性，炎症和“自身免疫性”男性因素不育：啮齿动物模型如何为临床实践提供依据？
影响因子：
13.3
作者：
Fijak M;Pilatz A;Hedger MP;Nicolas N;Bhushan S;Michel V;Tung KSK;Schuppe HC;Meinhardt A
通讯作者：
Meinhardt A
影响因子：
7.3
作者：
Fitzsimons S;Oggero S;Bruen R;McCarthy C;Strowitzki MJ;Mahon NG;Ryan N;Brennan EP;Barry M;Perretti M;Belton O
通讯作者：
Belton O