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bioRxiv · 10.1101/591313

M. leprae infects human keratinocytes via the interaction of laminin-5 with α-dystroglycan, integrin-β1, or -β4.

Jin, S.-H.·Kim, S.-K.·Lee, S.-B.
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Abstract

Although Mycobacterium leprae (M. leprae) is usually found in macrophages and nerves of the dermis of patients with multibacillary leprosy, it is also present in all layers of the epidermis, basal, suprabasal, prickle cells, and keratin layers. However, the mechanism by which M.leprae invades the dermis remains unknown, whereas the underlying mechanism by which M.leprae invades peripheral nerves, especially Schwann cells, is well defined. M. leprae binds to the -dystroglycan (DG) of Schwann cells via the interaction of -DG and laminin (LN)-2 in the basal lamina, thus permitting it to become attached to and invade peripheral nerves. In the current study, we investigated the issue of how M.leprae infects keratinocytes. LN-5 is the predominant form of laminin in the epidermis and allows the epidermis to be stably attached to the dermis via its interaction with /{beta}-DG as well as integrins that are produced by keratinocytes. We therefore focused on the role of LN-5 in when M. leprae invades keratinocytes. Our results show that M.leprae preferentially binds to LN-5-coated slides and this binding to LN-5 enhances its binding to human epidermal keratinocytes, neonatal (HEKn). The findings also show that pre-treatment with an antibody against -DG, integrin-{beta}1, or -{beta}4 inhibited the binding of LN-5-coated M.leprae to HEKn cells. These results suggest that M. leprae infects keratinocytes by taking advantage of the interaction of LN-5 in the basal lamina of the epidermis and a surface receptor of keratinocytes, such as -DG, integrin-{beta}1, or -{beta}4.\n\nAuthor summaryIn the current study, we investigated the issue of how M.leprae infects keratinocytes. We focused on the role of LN-5, a predominant form of laminin of the epidermis, in the invasion of M. leprae in keratinocytes. Our results show that M. leprae preferentially binds to LN-5-coated slides and coating M.leprae with LN-5 enhanced its binding to human epidermal keratinocytes, neonatal (HEKn). In addition, a pre-treatment with an antibody against -DG, integrin-{beta}1 or -{beta}4 inhibited the binding of LN-5-coated M. leprae to HEKn cells. These results suggest that M. leprae invades keratinocytes by taking advantage of the interaction of LN-5 in the basal lamina of the epidermis and a surface receptor of keratinocytes, such as -DG, integrin-{beta}1, or -{beta}4

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Jin, S.-H., Kim, S.-K., Lee, S.-B.. 2019-03-27. M. leprae infects human keratinocytes via the interaction of laminin-5 with α-dystroglycan, integrin-β1, or -β4.. https://doi.org/10.1101/591313

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