Introduction
Schistosomiasis is one of the most important parasite diseases, affecting over 200 million people in the world1, 2,3,4. It is caused by Schistosoma infection and the main disease-causing species are Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium. Schistosomiasis is the endemic in 78 countries in Africa, South America, and Asia, while Schistosomiasis japonica is mainly prevalent in Asia, particularly in China5. Although China has achieved tremendous successes in schistosomiasis control, China is still among the countries with the highest social and economic burden from schistosomiasis6,7,8.
According to the disease progression, schistosomiasis japonica is classically divided into three distinctive clinical stages: acute schistosomiasis, chronic schistosomiasis, and advanced schistosomiasis. Acute schistosomiasis occurs when people contact with water containing cercariae. Patients with acute schistosomiasis will typically have a fever, diarrhea, abdominal pain, fatigue, and malaise3,9,10,11. Chronic schistosomiasis japonica develops after years of infection, which is caused by immunopathological reactions and chronic inflammation in reaction to eggs produced by mature schistosomes. Advanced schistosomiasis is the most severe stage of schistosomiasis japonica, associated with poor survival and prognosis. Patients with advanced schistosomiasis are usually accompanied by liver fibrosis, portal hypertension, ascites, splenomegaly, and gastro-esophageal variceal bleeding, or with a granulomatous disease of the colon 1, 12, 13. As China is moving toward schistosomiasis elimination, very few acute schistosomiasis cases occur, however, there is still a large number of patients with chronic schistosomiasis or advanced schistosomiasis, representing a severe public health problem 6, 7. Furthermore, the underlying mechanism remains not well defined and there is a lack of effective treatment. Thus, further study is needed to deepen the understanding of the pathological mechanism and promote the elimination of schistosomiasis.
Schistosomiasis is associated with multiple mechanisms, among which immune cells play a critical role in the development of schistosomiasis14, 15. The immunological status varies in different phases of schistosomiasis. Studies have demonstrated that both Th1 and Th2 immune responses get involved in the pathogenesis of schistosomiasis 16, 17. In the initial phase of Schistosoma japonica infection, the immune responses are characterized by increased CD4+IFN-γ+T cells, TNF-α, and IL-618, 19. However, in the chronic schistosomiasis stage, the immune responses shift from Th1 to Th2/regulatory phenotype, featured by higher expression of Th2 associated cytokines, such as IL-4, IL-5, IL-13, and IL-1020. Shreds of evidence also suggested that CD4+CD25+Foxp3+Treg cells are increased in the stage of chronic schistosomiasis. In addition, higher expression of IL-17 was observed in this stage18, 21. Interestingly, lymphocytes from patients with advanced schistosomiasis didn’t show a higher production of Th2 cytokines or proinflammatory cytokines when compared with patients in other stages, which is associated with immune exhaustion22. T cells are not only critical in the pathogenesis of schistosomiasis, but they are also important for the resistance to infection. Studies showed that peripheral T cells declined when infected with Schistosoma, however deletion of T cells abolished the resistance to Schistosoma infection18. In addition to T cells, B cells are also involved in the development of schistosomiasis. The expansion of Breg cells in the peripheral blood is regarded as an important feature in patients with chronic schistosomiasis23, 24 As classic innate immune cells, NK cells also play a significant role in schistosomiasis22, 25-27. NK cells can negatively regulate Schistosoma japonica infection-induced liver fibrosis, as activated NK cells attenuated Schistosoma-induced liver fibrosis while deletion of NK cells dramatically enhanced liver fibrosis27.
Immune cells are important for the development of schistosomiasis japonica and are also critical for the treatment of schistosomiasis. The immune cells in the peripheral blood help assess the immune state. The peripheral lymphocytes in schistosomiasis mansoni were well studied, however immune cells in peripheral blood in patients with different stages of Schistosomiasis Japonica are not well analyzed. In this study, we analyzed T cells, B cells, and NK cells in peripheral blood in patients with schistosomiasis, using flow cytometry. We compared these profiles among healthy volunteers and patients in different stages of schistosomiasis japonica to assess the frequency and number of those immune cells in patients with schistosomiasis. In addition to this, we selected patients with well-documented clinical data and analyzed the ultrasound images of the patients in an attempt to find the relationship between peripheral lymphocytes and imaging of the patients.