PCV2 infection induces the differentiation of Treg cells via the TGF-β/Smad3 pathway.

In recent years, porcine circovirus type 2 (PCV2) has become a significant pathogenic virus in the swine industry, causing huge economic losses globally. However, the impact of PCV2 on the differentiation of CD4(+) T cells (Th1/Th2/Th17/Treg) remains unclear. In this study, we noticed that PCV2-infected piglets exhibited several clinical symptoms, including slow weight gain, diarrhea, and lethargy. In addition, we observed significant changes in the levels of IFN-γ, IL-4, and IL-17A during the early stages of infection, while the inhibitory cytokine IL-10 exhibited a significant increase in the later stages. Furthermore, the overall count of CD4(+) T helper cells was significantly reduced, and the Th1/Th2/Th17/Treg immune balance was disrupted, with a shift towards Treg cells. What is more, we revealed that TGF-β, a cytokine that induces Treg cell differentiation, was highly expressed after PCV2 infection. This cytokine recruited and phosphorylated Smad3, which subsequently translocated into the nucleus to facilitate Foxp3 transcription. Besides, we also investigated the association between the changes in the intestinal microbiota caused by PCV2 infection and the immune balance of T cells. Overall, our findings enriched the mechanism of PCV2 promoting Treg cell differentiation and provided valuable insights for the prevention and treatment of immunosuppressive diseases. IMPORTANCE: Porcine circovirus type 2 (PCV2) infection can cause immunosuppression-related diseases in pigs. Currently, it is still recognized as an important infectious pathogen of the swine industry in the world. In this study, we discovered that PCV2 infection disrupted the Th1/Th2/Th17/Treg immune equilibrium, and the differentiation capacity of Treg cells increased significantly. Briefly, PCV2 infection promoted the secretion of cytokine TGF-β, recruited Smad3, and phosphorylated it. Subsequently, the phosphorylated Smad3 transmitted the signal from the cell membrane to the nucleus and bound to the enhancer of Foxp3, thereby enhancing the transcription level of Foxp3 and facilitating the differentiation of Treg cells. This study enriches the pathogenic mechanism of PCV2 persistent infection and provided a theoretical basis for the prevention and control of immunosuppressive diseases.