Myelination key factor krox-20 is downregulated in Schwann cells and murine sciatic nerves infected by Mycobacterium leprae

Abstract

Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicate that Mycobacterium leprae (ML) regulates the expression of key factors related to SC identity, suggesting that alterations in cell phenotype may be involved in the pathogenesis of neural damage in leprosy. To better understand whether ML restricts the plasticity of peripheral nerves, the present study sought to determine the expression of Krox-20, Sox-10, c-Jun and p75NTR in SC culture and mice sciatic nerves, both infected by ML Thai-53 strain. Primary SC cultures were stimulated with two different multiplicities of infection (MOI 100:1; MOI 50:1) and assessed after 7 and 14 days. Sciatic nerves of nude mice (NU-Foxn1(nu)) infected with ML were evaluated after 6 and 9 months. In vitro results demonstrate downregulation of Krox-20 and Sox-10 along with the increase in p75NTR-immunolabelled cells. Concurrently, sciatic nerves of infected mice showed a significant decrease in Krox-20 and increase in p75NTR. Our results corroborate previous findings on the interference of ML in the expression of factors involved in cell maturation, favouring the maintenance of a non-myelinating phenotype in SCs, with possible implications for the repair of adult peripheral nerves.