TGF-β/Smad signaling pathway regulates Th17/Treg balance during Echinococcus multilocularis infection

- Mice model infected with Echinococcus multilocularis (Em) is established.
- Dynamic expression of TGF-β/Smad signaling proteins, Treg and Th17 cells is studied.
- TGF-β and Smad7 increased in early infection while Smad2/3 in middle-late infection.
- Levels of Treg cells, Foxp3, Th17 cells, RORγt are higher in middle infection.
- Treg and Th17 are involved in Em infection and regulated by TGF-β/Smad signaling.

Alveolar echinococcosis (AE) is a severe parasitic disease caused by the infection of Echinococcus multilocularis (Em). Very little is known on the relationship between TGF-β/Smad signaling pathway and Treg/Th17 balance in the infected liver at different periods after Em infection. Using qRT-PCR, immunohistochemistry, flow cytometry and CBA assay, we measured the expression levels of TGF-β, Smad2/3/7, ROR-γt, Foxp3, IL-17, IL-10 and percentages of Th17 cells and Treg cells in mouse AE model, from day 2 to day 270 after infection. In the early stage of infection (day 2 to day 30), Smad7 was up-regulated and the TGF-β pathway was inactivated. In the middle stage of infection (day 30 to day 90), TGF-β and Smad2/3 were up-regulated. And levels of Treg cells, Foxp3, Th17 cells, RORγt, IL-17, IL-10 and IL-6 were significantly increased. In the late stage of infection (day 90 to day 270), Treg cells, Foxp3, TGF-β and IL-10 maintained at high levels whereas Th17 cells and IL-17 decreased significantly. TGF-β/Smad signaling pathway was activated during the chronic infection. Our data suggest that there were Treg/Th17 imbalance in the middle and especially in the late stage of Em infection and that Treg/Th17 imbalance may be regulated by TGF-β/Smad signaling pathway. Treg and Th17 subsets may be involved in regulating immune tolerance and tissue inflammation, and facilitating the long-term survival of Em in the host.