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.
Highlights
CD4+ T cells play an important role in the initiation of immune responses against an infection by providing help to other cells and by taking on a variety of effector functions during immune reactions
Our 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
These results indicated that all of the CD4+ T cell subsets (Th17, Th1, Th2 and T regulatory (Treg) cells) increased as over the course of infection
Summary
CD4+ T cells play an important role in the initiation of immune responses against an infection by providing help to other cells and by taking on a variety of effector functions during immune reactions. Th17 cells recently emerged as a third independent effector cell subset differentiated from CD4+ T cells upon antigenic stimulation [2,3,4,5]. The functions of these cell subtypes are not completely understood, emerging data suggest that by producing their defining cytokine IL-17, Th17 cells play an important role in host defenses against extracellular pathogens, such as Klebsiella pneumoniae [6], Pseudomonas aeruginosa [7], Porphyromonas gingivalis [8] and Bacteroides fragilis [9], which are not efficiently cleared by Th1-type and Th2type immunity. CD4+ T cells play critical roles in both host immune responses against parasitic infection and immunopathology in schistosomiasis. 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
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