Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 115 | JUNE 2020
Effect of Mycobacterium leprae on Neurotrophins Expression in Human Schwann Cells and Mouse Sciatic Nerves [ACCEPTED ARTICLES / PRELIMINARY VERSION]
1Lauro de Souza Lima Institute, São Paulo State Health Secretariat, Bauru, Brasil
2Biological Sciences Department, Bauru School of Dentistry, University of São Paulo, Bauru, Brasil
3Immunopathology Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brasil
4Cellular Microbiology Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Brasil
BACKGROUND Although Mycobacterium leprae (ML) is well characterized as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral
nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity.
OBJECTIVES We aimed to investigate the effect of ML on neurotrophins expression in human SC and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches.
METHODS Firstly, we evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in human SC from amputation nerve fragments. In vivo experiments, athymic nude mice were infected by ML for eight months.
FINDINGS and MAIN CONCLUSIONS Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.