Work

Single-cell analysis reveals shared and stage-specific features of the human skin response in primary and secondary syphilis lesions

Year: 2026

Type: preprint

Abstract: Syphilis, caused by Treponema pallidum subspecies pallidum (TPA), is a resurging global health threat whose complex immunobiology is poorly recapitulated by animal models. We integrated single-cell transcriptomics with tissue and cellular analyses to define immune responses in freshly obtained skin and blood during primary and secondary syphilis. IL1B⁺ macrophages dominated the macrophage infiltrate and, together with dendritic cells, exhibited peak activation in primary lesions, coinciding with heightened inflammatory and cytotoxic CD4⁺ and CD8⁺ T cell responses. GZMK_CD8_T cells were the principal source of IFNG across disease stages. TPA-specific plasma cells populated lesions, yet B cell affinity maturation and class-switch recombination were impaired during primary syphilis, revealing a potential mechanism of ineffective humoral immunity. Stage-specific immune remodeling was further shaped by coordinated communication among immune and stromal cells. Together, our findings provide a systems-level framework for understanding how robust immune activation coexists with immune evasion during early syphilis.

Source: Research Square

DOI: 10.21203/rs.3.rs-10765906/v1