Jin Song-Hyo, An Sung-Kwan, Lee Seong-Beom
Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, Republic of Korea.
Research Institute for Molecular-targeted Drugs, Department of Cosmetics Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea.
PLoS Negl Trop Dis. 2017 Jun 21;11(6):e0005687. doi: 10.1371/journal.pntd.0005687. eCollection 2017 Jun.
Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells.
麻风病是一种慢性传染病,由专性细胞内病原体麻风分枝杆菌(M.leprae)引起,它是全球所有非创伤性周围神经病变的主要原因。在瘤型麻风病患者中,虽然有髓鞘和无髓鞘雪旺细胞均会被麻风分枝杆菌感染,但该菌更倾向于侵入无髓鞘雪旺细胞。然而,麻风分枝杆菌感染对无髓鞘雪旺细胞的影响尚未阐明。在瘤型麻风病患者的神经活检中,发现被麻风分枝杆菌感染的雪旺细胞内有脂滴(LDs)。麻风分枝杆菌诱导的脂滴形成有利于原代雪旺细胞和一种被称为ST88 - 14的有髓鞘雪旺细胞系中细胞内麻风分枝杆菌的存活。在本研究中,我们首先对SW - 10细胞进行了表征,并研究了脂滴对被麻风分枝杆菌感染的SW - 10细胞(即无髓鞘雪旺细胞)的影响。SW - 10细胞表达S100(一种神经嵴来源细胞的标志物)和NGFR p75(一种未成熟或无髓鞘雪旺细胞的标志物)。然而,SW - 10细胞不表达髓鞘碱性蛋白(MBP,一种有髓鞘雪旺细胞的标志物)和髓鞘蛋白零(MPZ,一种前体、未成熟或有髓鞘雪旺细胞的标志物),所有这些都表明SW - 10细胞是无髓鞘雪旺细胞。此外,SW - 10细胞具有吞噬活性,并且可被麻风分枝杆菌感染。麻风分枝杆菌感染会诱导脂滴的形成。此外,抑制麻风分枝杆菌诱导的脂滴形成会增强含有活麻风分枝杆菌的吞噬体的成熟,并降低SW - 10细胞中麻风分枝杆菌的ATP含量。这些事实表明,麻风分枝杆菌形成的脂滴有利于其在SW - 10细胞内的存活,由此得出合理结论,即被麻风分枝杆菌感染的SW - 10细胞可成为研究麻风分枝杆菌与无髓鞘雪旺细胞相互作用的新模型。