Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Cell Microbiol. 2020 Jan;22(1):e13128. doi: 10.1111/cmi.13128. Epub 2019 Nov 13.
Leprosy neuropathy is a chronic degenerative infectious disorder of the peripheral nerve caused by the intracellular obligate pathogen Mycobacterium leprae (M. leprae). Among all nonneuronal cells that constitute the nerve, Schwann cells are remarkable in supporting M. leprae persistence intracellularly. Notably, the success of leprosy infection has been attributed to its ability in inducing the demyelination phenotype after contacting myelinated fibres. However, the exact role M. leprae plays during the ongoing process of myelin breakdown is entirely unknown. Here, we provided evidence showing an unexpected predilection of leprosy pathogen for degenerating myelin ovoids inside Schwann cells. In addition, M. leprae infection accelerated the rate of myelin breakdown and clearance leading to increased formation of lipid droplets, by modulating a set of regulatory genes involved in myelin maintenance, autophagy, and lipid storage. Remarkably, the blockage of myelin breakdown significantly reduced M. leprae content, demonstrating a new unpredictable role of myelin dismantling favouring M. leprae physiology. Collectively, our study provides novel evidence that may explain the demyelination phenotype as an evolutionarily conserved mechanism used by leprosy pathogen to persist longer in the peripheral nerve.
麻风病神经病变是一种由细胞内专性病原体麻风分枝杆菌（M. leprae）引起的慢性进行性感染性周围神经疾病。在构成神经的所有非神经元细胞中，许旺细胞在支持麻风分枝杆菌在细胞内持续存在方面表现出色。值得注意的是，麻风病感染的成功归因于其在接触有髓纤维后诱导脱髓鞘表型的能力。然而，麻风分枝杆菌在持续的髓鞘破坏过程中的确切作用尚完全不清楚。在这里，我们提供的证据表明麻风病病原体对许旺细胞内退化的髓鞘空泡有一种意外的偏好。此外，麻风分枝杆菌感染通过调节一组参与髓鞘维持、自噬和脂质储存的调节基因，加速了髓鞘分解和清除的速度，导致脂质滴的形成增加。值得注意的是，髓鞘分解的阻断显著降低了麻风分枝杆菌的含量，这表明髓鞘解体的新的不可预测的作用有利于麻风分枝杆菌的生理学。总之，我们的研究提供了新的证据，可能解释脱髓鞘表型是麻风病病原体在周围神经中持续存在的一种进化上保守的机制。
