Abstract
Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis.
Highlights
Clonorchiasis is a disease affecting about 15 million people; it is caused by Clonorchis sinensis that is widely distributed in east and southeast Asia including Korea, China, Russia, and Vietnam [1,2]
The frequencies of Th17 and Treg in CD4+ T cells steadily increased as the infection developed, and significant differences were observed on day 56 PI, compared with the control group (P
We and others have demonstrated that this strain is relatively susceptible to C. sinensis infection compared with ICR, DDY, cytometric bead array (CBA)/N, C57BL/6, and C3H/HeN mice [30,31,32]
Summary
Clonorchiasis is a disease affecting about 15 million people; it is caused by Clonorchis sinensis that is widely distributed in east and southeast Asia including Korea, China, Russia, and Vietnam [1,2]. People can become infected by ingesting raw or undercooked freshwater fish containing infective C. sinensis metacercariae. Digestive juice in the duodenum stimulate the swallowed metacercariae to excyst, and the fresh C. sinensis juveniles move to the intrahepatic bile duct where they grow into adult worms and can live for decades [3,4]. Chronic C. sinensis infection can result in pathological changes such as biliary duct proliferation, inflammation. The Imbalance of Treg and Th17 in Clonorchis sinensis-Infected Mice. Foundation of Xuzhou Medical College (Grant Nos. 2014KJ08 and 2014KJ10). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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