School of Medicine of Botucatu, São Paulo State University, Botucatu, Brazil.
Lauro de Souza Lima Institute, Secretariat of Health of São Paulo, Bauru, São Paulo, Brazil.
Int J Exp Pathol. 2019 Apr;100(2):83-93. doi: 10.1111/iep.12309. Epub 2019 May 14.
Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicate that Mycobacterium leprae (ML) regulates the expression of key factors related to SC identity, suggesting that alterations in cell phenotype may be involved in the pathogenesis of neural damage in leprosy. To better understand whether ML restricts the plasticity of peripheral nerves, the present study sought to determine the expression of Krox-20, Sox-10, c-Jun and p75NTR in SC culture and mice sciatic nerves, both infected by ML Thai-53 strain. Primary SC cultures were stimulated with two different multiplicities of infection (MOI 100:1; MOI 50:1) and assessed after 7 and 14 days. Sciatic nerves of nude mice (NU-Foxn1 ) infected with ML were evaluated after 6 and 9 months. In vitro results demonstrate downregulation of Krox-20 and Sox-10 along with the increase in p75NTR-immunolabelled cells. Concurrently, sciatic nerves of infected mice showed a significant decrease in Krox-20 and increase in p75NTR. Our results corroborate previous findings on the interference of ML in the expression of factors involved in cell maturation, favouring the maintenance of a non-myelinating phenotype in SCs, with possible implications for the repair of adult peripheral nerves.
许旺细胞 (SCs) 对维持周围神经系统的可塑性至关重要。周围神经损伤和感染会刺激 SCs,以恢复神经组织的内稳态。先前的研究表明,麻风分枝杆菌 (ML) 调节与 SC 特性相关的关键因子的表达,表明细胞表型的改变可能与麻风病中神经损伤的发病机制有关。为了更好地了解 ML 是否限制周围神经的可塑性,本研究旨在确定 Krox-20、Sox-10、c-Jun 和 p75NTR 在 ML 泰国-53 株感染的 SC 培养物和小鼠坐骨神经中的表达。用两种不同的感染复数 (MOI 100:1;MOI 50:1) 刺激原代 SC 培养物,并在 7 天和 14 天后进行评估。感染 ML 的裸鼠 (NU-Foxn1) 的坐骨神经在 6 个月和 9 个月后进行评估。体外结果表明 Krox-20 和 Sox-10 的下调以及 p75NTR 免疫标记细胞的增加。同时,感染小鼠的坐骨神经中 Krox-20 显著减少,p75NTR 增加。我们的结果证实了先前关于 ML 干扰参与细胞成熟的因子表达的发现,有利于 SC 中无髓鞘表型的维持,这可能对成年周围神经的修复有影响。