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.