TPx Protein of Cysticercus cellulosae Regulates Macrophage M2 Polarization via the cGMP-PKG Signaling Pathway

Cysticercosis, caused by the larval stage of Taenia solium (Cysticercus cellulosae), is a neglected tropical disease threatening public health. Thioredoxin peroxidase (TPx) is a key antioxidant protein secreted by the parasite, but its role in macrophage polarization remains unclear. In this study, THP-1-derived macrophages were treated with TPx protein for 24 h and 48 h. Flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were employed to assess reactive oxygen species (ROS) levels, M1/M2 cell proportions, mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10), and protein expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). Transcriptome sequencing was performed to screen for signaling pathways, and enzyme-linked immunosorbent assay (ELISA) was subsequently used to measure cGMP levels. The PKG inhibitor KT-5823 was used for functional validation. The results show that TPx significantly increased the proportion of M1 macrophages from 4.58% to 9.24% at 24 h, and promoted M2 macrophages from 4.12% to 6.87% at 48 h, while ROS levels decreased to 0.80-fold at 48 h (p < 0.05). RT-qPCR revealed that TPx markedly upregulated TNF-α (1.62-fold) at 24 h and IL-10 (1.52-fold) at 48 h (p < 0.05). Western blot showed that TPx increased iNOS expression by 2.55-fold at 24 h and Arg-1 expression by 2.01-fold at 48 h. KEGG analysis revealed upregulation of the cGMP-PKG pathway at 48 h, with notably increased cGMP content (1.48-fold) and PKG expression (1.86-fold) (p < 0.05). Furthermore, KT-5823 pretreatment effectively reversed TPx-induced Arg-1 upregulation (from 1.66-fold to 1.02-fold, p < 0.05). These findings demonstrate that Cysticercus cellulosae TPx induces M1 polarization at 24 h and promotes M2 polarization at 48 h through activation of the cGMP-PKG signaling pathway, thereby facilitating immune evasion.