Abstract

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.

Highlights

  • Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae)

  • Our results show that SW-10 cells are non-myelinating Schwann cells

  • Inhibition of M. leprae-induced Lipid droplets (LDs) formation enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content of M. leprae in SW-10 cells, suggesting that LD formation by M. leprae favors M. leprae survival in SW-10 cells

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Summary

Introduction

Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae). The introduction of multidrug therapy (MDT) to leprosy program in 1982 resulted in a significant reduction in the prevalence of the disease, 210,758 new leprosy cases were detected globally in 2014 [1]. Leprosy is the leading cause of all non-traumatic peripheral neuropathies worldwide. M. leprae almost exclusively infects macrophages and Schwann cells. The Schwann cells, the principal glial cells of the peripheral nervous system, provide support and nutrition to the axons of neurons and are a major target of M.leprae. Physical contact of M.leprae to Schwann cells and immune reactions against either M.leprae or the infected cells damage the peripheral nerves, which results in a demyelination of the peripheral nerve fibers, and leads to irreversible nerve damage [2,3,4,5]

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