The Dynamic Expression Of Induced IL-17 And IL-23 From Mice Infected With Schistosoma Japonicum

Among human parasitic diseases, schistosomiasis is a globle disease which ranks second behind malaria in harms of socia-economic and public health. It is still spreading in 76 developing countries, mostly in Asia, Africa, and Latin America. There are three schistosome species with most clinical importance. In China, the species responsible is Schistosoma japonicum. Currently, more than 760 thousand people are in risk of infection, especially people in rural and peri-urban areas.Since schistosomiasis is a pandemic disease, studies of vaccines against Schistosoma become an important method for control of the disease. Six candidated vaccines against Schistosoma were recommended by WHO, paramyosin, glutathione S-transferase (GST), glyceraldehyde 3-phosphate dehydrogenase (SG3PDH), fatty acid binding protein, triose phosphate-isomerase (TPI) and irradiated vaccine, but they fail to yield enough protective immunity. So further understanding in the immune effect mechanisms against schistosomiasis is a critical basement of vaccine development. As we know, effective immunization genetated antigen-specific CD4+ T cell response (Th1/Th2) which play a crucial role in the host defense against schistosome.Recently, a novel subset of CD4+ cell, Th17 lymphocytes, have been indentified. Distinctd from products of the Th1 and Th2 lineages, Th17 cells mainly produce IL-17A,IL-17F,IL-21 and IL -22, and IL-17A plays an important role in host defense and autoimmune diseases. Recent study found that the orphan nuvlear receptor (RORγt) is the key transcription factor that orchestrates the differentiation of Th17 cell. During this differentiation, TGF-βand IL-6 launche the process firstly, IL-21 produced by Th17 cells drives IL-17 production in an autocrine manner. TGF-βand IL-6 can activate STAT3, which sequently induces the expression of RORγt. IL-23 is an important cytokine for the maintenance of Th17. Lacking of IL-23 does not affect the production of Th17, but Th17 can not proliferate and survive. Effective infection can induce the expression of IL-23 by activating macrophages and other antigen presenting cells, so infection can promote the survival of Th17. Th17 is an effector T cells essential for the development of the inflammation. Recent study found that variety of microoganisms induced the exprssion of IL-17 in the early stage of the infection. After the ligation of IL-17 and IL-17R, many receptor cells such as granulocyte cells, epithelial cells and fibroblasts were induced to express some cytekines and chemokines, which led to the develpment and activation of neutrophils. Neutrophils were recruited to the site of infection and played a role in host defense. In addition, IL-17 could induce the production of other T cells, e.g. Th1, TDTH. Overall, L-23/IL-17 axis has become a hot topic in current study. In our study, we investigated the expression of L-23/IL-17 axis in schistosoma japonicum infection by detecting the protein and mRNA levels of IL-17A and IL-23p19 in splenocytes.BALB/c mice were transcutaneously infected with 25 S. japonicum cercaria. Spleen tissues and supernatant of splenic cells were isolated at 0, 1, 2, 4, 6, 8, and 10 weeks after infection. The worm burden was checked in order to verify the situation of infection. In the result, all the infected mice from 4-10 weeks groups shared similar worm burden, which confirmed a corherence of immune environment.Sandwich ELISA was used to measure the expression of IL-17A and IL-23p19 in supernatant of splenic cells with ConA incubation. And, we further detected mRNA level of 17A and IL-23p19 in spleen tissues. In infection groups, the level of IL-17A and IL-23p19 gradually increased compared with the control mice, and reached the peak at 1 week after infection (187.87pg/ml). The IL-17A production reduced to normal level at 4 week after infection, and was even lower at 6 week post-infection. Consistent with the dynamic expression of IL-17A, the IL-23p19 expression increased at 1 week post-infection, but it went up to the peak at 2 week post-infection and gradually reduced into the normal level at 4 week. Morever, IL-23p19 expression remained relatively low at 8week after infection. These results demostrated the early stage of infection led to the increased expression of IL-17A and IL-23p19. IL-17A and IL-23p19 mRNA were detected from the first week after infection, and significantly higher expressed compared with the control. For both IL-17A and IL-23p19, the dynamic change of mRNA was coincident, as Spearman's Rank Correlation Test revealed that there was a significant positive correlation between them.The purpose of this study was to detect the dynamic expression of IL-17A and IL-23p19 in BALB/c mice with the infection of schistosoma japonicum. We concluded that IL-17A and IL-23p19 were co-expression in the mice after infection. There was a significant increase in the early stage of infection. IL-17A and IL-23p19 may play an important role during the immune process in the very early stage of Schistosoma infection.