BACKGROUND Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS and MAIN CONCLUSIONS Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.

中文翻译：

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麻风分枝杆菌对人雪旺细胞和小鼠坐骨神经中神经营养蛋白表达的影响。

背景虽然麻风分枝杆菌（ML）被明确描述为麻风病的病原体，但周围神经损伤的病理生理机制仍需要进一步了解。体外和体内研究深入了解了 ML 与雪旺细胞 (SC) 相互作用的分子机制，表明对神经可塑性至关重要的基因和蛋白质的调节。目的 我们旨在研究 ML 对人 SC (hSC) 和小鼠坐骨神经中神经营养蛋白表达的影响，以更好地了解它们在麻风神经病中的作用，并旨在为未来的治疗方法做出贡献。方法 我们评估了来自截肢神经片段的 hSC 以及 ML 感染八个月的无胸腺裸鼠中 BDNF、NGF、NT-3、NT-4 的 mRNA 和蛋白表达。结果和主要结论我们的体外结果显示，与对照组相比，ML 处理的 hSC 中 NGF 和 BDNF mRNA 呈下降趋势。在 ML 处理的 hSC 中，BDNF 和 NT-4 的免疫检测显着下调。相反，与未感染的动物相比，ML 感染的小鼠表现出 NT-3 的上调。我们的研究结果表明，ML 可能参与神经营养因子的调节，这表明这些生长因子与病原体相关的不平衡可能在麻风病的神经损伤中发挥作用。