Treponema pallidum-induced prostaglandin E2 secretion in skin fibroblasts leads to neuronal hyperpolarization: A cause of painless ulcers.

Abstract

Primary syphilis is characterized by painless ulcerative lesions in the genitalia, the aetiology of painless remains elusive. To investigate the role of Treponema pallidum in painless ulcer of primary syphilis, and the mechanisms underlying painless ulcers caused by T. pallidum. An experimental rabbit model of primary syphilis was established to investigate its effects on peripheral nerve tissues. Human skin fibroblasts were used to examine the role of T. pallidum in modulating neurotransmitters associated with pain and to explore the signalling pathways related to neurotransmitter secretion by T. pallidum invitro. Treponema pallidum infection did not directly lead to neuronal damage or interfere with the neuronal resting potential. Instead, it facilitated the secretion of prostaglandin E2 (PGE2) through endoplasmic reticulum stress in both rabbit and human skin fibroblasts, and upregulation of PGE2 induced the hyperpolarization of neurones. Moreover, the IRE1α/COX-2 signalling pathway was identified as the underlying mechanism by which T. pallidum induced the production of PGE2 in human skin fibroblasts. Treponema pallidum promotes PGE2 secretion in skin fibroblasts, leading to the excitation of neuronal hyperpolarization and potentially contributing to the pathogenesis of painless ulcers in syphilis.