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Background: Primary syphilis is characterized by painless ulcerative lesions in the genitalia, the aetiology of painless remains elusive. Objectives: To investigate the role of Treponema pallidum in painless ulcer of primary syphilis, and the mechanisms underlying painless ulcers caused by T. pallidum. Methods: 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 in vitro. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: During Treponema pallidum (T. pallidum) infection, the host's immune system actively engages in pursuit and elimination of T. pallidum, while T. pallidum skillfully employs various mechanisms to evade immune recognition. Macrophages exhibit incomplete clearance of T. pallidum in vitro and the underlying mechanism of how T. pallidum resists the attack of macrophage remains unclear. Objectives: To investigate the effect of T. pallidum membrane protein Tp47 on the phagocytosis of macrophages. Methods: THP‐1‐derived macrophages were used to investigate the role of Tp47 in the secretion of Prostaglandin E2 (PGE2) in macrophages and the mechanism by which Tp47 induced the production of PGE2, as well as the impact of PGE2 on the macrophage's phagocytosis. Results: Tp47 (1–10 μg/mL) significantly inhibited the phagocytosis of latex beads and T. pallidum in macrophages (p ≤ 0.05). PGE2 production by macrophages could be induced by Tp47, and the phagocytic function of macrophages could be restored using PGE2 antibody. Tp47 produced PGE2 by activating the PERK/NF‐κB/COX‐2 pathway in macrophages. Inhibitors targeting PERK, NF‐κB and COX‐2, respectively, reduced the level of PGE2 and restored the phagocytic function of macrophages. Conclusion: Tp47‐induced PGE2 production via the PERK/NF‐κB/COX‐2 pathway contributed to macrophage phagocytosis inhibition, which potentially contributes to immune evasion during the T. pallidum infection. [ABSTRACT FROM AUTHOR]