The TPx Protein of Cysticercus cellulosae Promotes an IL-10-Producing Regulatory B Cell Phenotype in Human B...

Thioredoxin peroxidase (TPx) derived from Taenia solium cysticerci (Cysticercus cellulosae) mediates immune evasion by disrupting T cell subset homeostasis. However, its effect on regulatory B cells (Bregs) and the underlying mechanism remain unknown. We stimulated GM12878 B cells with TPx and assessed Breg differentiation by flow cytometry, ELISA, and RT-qPCR. We evaluated the function of TPx-pretreated B cells in co-culture with T cells. We then combined RNA sequencing, Western blot, ELISA, and pharmacological inhibition to identify the signaling pathway involved. TPx increased the CD19⁺CD24^hiCD27⁺ Breg subset in a time-dependent manner, peaking at 72 h. This effect was accompanied by enhanced IL-10 secretion and upregulated transcription of IL-10, TGF-β, and IL-35. TPx-pretreated B cells reduced CD4⁺ T-cell blastogenesis (cell size) and the CD4⁺ fraction of the co-culture and increased the frequency of cells with a CD4⁺CD25⁺CD127^- Treg-like surface phenotype. RNA sequencing identified cAMP-related pathways as central to this process. TPx elevated intracellular cAMP and activated the PKA/CREB phosphorylation cascade, whereas the adenylyl cyclase inhibitor SQ22536 reversed TPx-induced Breg differentiation and IL-10 secretion. In this human B cell line model, TPx promotes acquisition of a Breg-like phenotype in an adenylyl cyclase-dependent manner, revealing a novel mechanism of cysticercosis-associated immune evasion.