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Abstract

Front cover Axonopathy is considered a hallmark of leprosy neuropathy, a chronic infectious disease caused by Mycobacterium leprae infection in Schwann cells. Leprosy neuropathy is associated with irreversible motor and sensory loss seen in infected patients. In the present work, immortalized human Schwann cell line ST8814 were infected with M.leprae. The neurotoxicity of infected Schwann cell-conditioned medium (SCCM) was then evaluated in a human neuroblastoma cell lineage and mouse neurons. ST8814 Schwann cells exposed to M. leprae affected neuronal viability by deviating glial 14C-labeled lactate, important fuel of neuronal central metabolism, to de novo lipid synthesis. We observed that transgenic M. bovis (BCG) cells expressing the M. leprae phenolic glycolipid-1 (PGL-1), a specific cell wall antigen proposed to mediate bacterial-Schwann cell interaction - (BCG-PGL-1) - was able to induce a phenotype similar to M. leprae, unlike the wild type BCG strain. This Schwann cell neurotoxic phenotype, induced by M. leprae PGL-1, occurs through the protein kinase B (Akt) pathway. The pharmacological inhibition of Akt by triciribine significantly reduced free fatty acid content in the SCCM from M. leprae- and BCG-PGL-1-infected Schwann cells and, hence, prevented neuronal death. Overall, these findings provide novel evidence that both M. leprae and PGL-1 induce a toxic Schwann cell phenotype, by modifying the host lipid metabolism, resulting in profound implications for neuronal loss as a basis of leprosy neuropathy. Image content Sensory neurons dissociated from mouse dorsal root ganglion, visualized by immunofluorescence using anti-ß-III tubulin evidencing neurotoxicity of M. leprae-infected Schwann cells conditioned medium over arborization. Read the full article ‘Phenolic glycolipid-1 of Mycobacterium leprae is involved in human Schwann cell line ST8814 neurotoxic phenotype’ by K. do Carmo de Vasconcelos Girardi, B. S. Mietto, K. dos Anjos Lima, G. C. Atella, D. S. da Silva, A. M. R. Pereira, P. S. Rosa, F. A. Lara. 2023, vol.164 (2), pp. 158–171) on doi:10.1111/jnc.15722