The role of iron in the course of bacterial infection of the testis

铁在睾丸细菌感染过程中的作用

• 批准号: 424111918
• 负责人: Professor Dr. Andreas Meinhardt
• 金额: --
• 依托单位: Institut für Anatomie und Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/424111918?language=en
• 关键词: role; iron; course; bacterial; infection

A major cause for environmentally induced male infertility is related to acute infectious epididymo-orchitis elicited by bacteria such as Neisseria gonorrhoeae, Chlamydia trachomatis or the uropathogenic E. coli (UPEC). Following UPEC infection, a reduction of epididymal sperm counts was observed also long after the resolution of the infection, which suggests a testicular involvement and possible damage to germ cells. UPEC has an exceptionally large range of iron acquisition systems which enable it to survive in extremely iron poor environments. In collaborative preparatory work, we have demonstrated that iron trafficking proteins are polarized in Sertoli cells and may participate in an internal iron cycle, which provides a constant controlled supply of iron to early developing germ cells to protect the developing sperm from oxidative stress and peripheral iron as well as nutrient fluctuations in general. We thus hypothesize, that UPEC infection will perturb the testicular iron homeostasis through UPEC elicited manipulation of host-iron regulatory proteins, directly affecting the host iron homeostasis and that the UPEC-elicited shift in iron homeostasis in the testis contributes to the course of the infection and male fertility. To test this hypothesis, the Meinhardt and Meyron-Holtz labs, experts in immunology of the male reproductive tract and iron metabolism, respectively, have teamed up. We will use an established mouse-model for UPEC mediated epididymo-orchitis to test how the infection with hemolysin A (hemolysin A is a pore forming protein important for iron acquisition of UPEC) positive or hemolysin A negative UPEC-strains will affect iron homeostasis, the course of the infection and fertility parameters in these mice. Understanding the contribution of iron homeostasis to male fertility during UPEC infection may lead to novel treatment strategies and the improvement of male fertility, following UPEC infection.

环境诱导的男性不育的一个主要原因是由细菌引起的急性感染性附睾-睾丸炎，如淋病奈瑟氏菌、沙眼衣原体或尿路致病性大肠杆菌。大肠杆菌（UPEC）。在UPEC感染后，在感染消退后很长时间内也观察到附睾精子计数减少，这表明睾丸受累并可能损害生殖细胞。UPEC拥有非常广泛的铁采集系统，使其能够在铁含量极低的环境中生存。在合作准备工作中，我们已经证明，铁运输蛋白在支持细胞中被极化，并可能参与内部铁循环，为早期发育的生殖细胞提供恒定的受控铁供应，以保护发育中的精子免受氧化应激和外周铁以及一般营养波动的影响。因此，我们假设，UPEC感染将扰乱睾丸铁稳态通过UPEC引起的主机铁调节蛋白的操纵，直接影响主机铁稳态和UPEC引起的转变，在睾丸铁稳态的感染和男性生育力的过程中作出贡献。为了验证这一假设，Meinhardt和Meyron-Holtz实验室，分别是男性生殖道免疫学和铁代谢的专家，已经联合起来。我们将使用已建立的UPEC介导的附睾-睾丸炎的小鼠模型来测试溶血素A（溶血素A是对UPEC的铁获取重要的成孔蛋白）阳性或溶血素A阴性UPEC菌株的感染将如何影响这些小鼠中的铁稳态、感染过程和生育力参数。了解UPEC感染期间铁稳态对男性生育力的贡献可能会导致UPEC感染后新的治疗策略和男性生育力的改善。