Dynamics of Th17 Cells and Their Role in Schistosoma japonicum Infection in C57BL/6 Mice

Abstract

BackgroundThe current knowledge of immunological responses to schistosomiasis, a major tropical helminthic disease, is insufficient, and a better understanding of these responses would support vaccine development or therapies to control granuloma-associated immunopathology. CD4+ T cells play critical roles in both host immune responses against parasitic infection and immunopathology in schistosomiasis. The induction of T helper (Th)1, Th2 and T regulatory (Treg) cells and their roles in schistosome infections are well-illustrated. However, little in vivo data are available on the dynamics of Th17 cells, another important CD4+ T cell subset, after Schistosoma japonicum infection or whether these cells and their defining IL-17 cytokine mediate host protective responses early in infection.MethodologyLevels of Th17 and the other three CD4+ T cell subpopulations and the cytokines related to induction or repression of Th17 cell generation in different stages of S. japonicum infection were observed. Contrary to reported in vitro studies, our results showed that the Th17 cells were induced along with the Th1, Th2, Treg cells and the IFN-γ and IL-4 cytokines in S. japonicum infected mice. The results also suggested that S. japonicum egg antigens but not adult worm antigens preferentially induced Th17 cell generation. Furthermore, decreasing IL-17 with a neutralizing anti-IL-17 monoclonal antibody (mAb) increased schistosome-specific antibody levels and partial protection against S. japonicum infection in mice.ConclusionsOur study is the first to report the dynamics of Th17 cells during S. japonicum infection and indicate that Th17 cell differentiation results from the integrated impact of inducing and suppressive factors promoted by the parasite. Importantly, our findings suggest that lower IL-17 levels may result in favorable host protective responses. This study significantly contributes to the understanding of immunity to schistosomiasis and may aid in developing interventions to protect hosts from infection or restrain immunopathology.

Ellagic acid reduces murine schistosomiasis mansoni immunopathology via up-regulation of IL-10 and down-modulation of pro-inflammatory cytokines production

“…On the other hand, Kang et al 110 reported that EA enhances production IgG subclass (IgG2a, IgG2b and IgG3). It has been shown that administration of anti-IL-17 neutralizing mAb significantly increased SEA-specific IgG, but the other antibodies did not change significantly 95,111 . Herein, we demonstrated that EA treatment decreased IL-17 production.…”

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells

“…In addition, S. mansoni worm infection depended on an IL-10-producing B cell population that prevented allergic hypersensitivity (Amu et al 2010;Mangan et al 2004). SEA and SWAP are two crucial sources of antigens exposed to the host during Schistosoma infection, both being capable of inducing Th1, Th2, Th17, and Treg cells and the corresponding cytokines (Pearce and MacDonald 2002;Wen et al 2011). The composition of SEA and SWAP is different.…”

“…We found that the IL-10 production of B cells in SEA-immunized mice was less than that in the B cells stimulated by SEA in vitro. When the mice immunized with SEA or SWAP, SEA preferentially induce a significant increase of Th2, Th17, and Treg cells (Wen et al 2011). These cells and the cytokines may have a suppressive effect on regulatory B cells, such as the Treg cells could suppress B cell activation and expansion (Lim et al 2005;Wang and Zheng 2013).…”

Association of Pneumococcal Carriage and Expression of Foxp3+ Regulatory T Cells and Th17 Cells in the Adenoids of Children

“…IL-17A released by Th17 cells was reported to have a host protective role during infections and chronic carriage of S. pneumoniae in animal models [17] . Delayed clearance and chronic pneumococcal carriage were first identified in IL-17 knockout mice [18,19] . A recent study [20] demonstrated a protective role for Th17 cells against pneumococcal carriage.…”