In Vitro Studies Of Interaction Between Schistosoma Japonicum Antigens And Antigen Presenting Cells

Nowdays, schistosomiasis japonica is still one of the main public health problems in our country. Although the comprehensive measures based on the principle of disease transmission ecology were valid, the effectiveness is difficult to be consolidated. Based on the incomparable virtue of vaccine in controlling of many infectious diseases, anti-schistosomiasis vaccine development has been the objective of scientists in the world for past half century. Even with long-term endeavor, there is no effective anti-schistosome infection vaccine so far. Currently, some of the immunological phenomena and the related molecular mechanisms of Schistosoma japonicum infection are still unclear,which greatly limited our ability to choose the better tactic and approaches for developing anti-schistosomiasis vaccines.Attenuated schistosome cercaria vaccine could induce relatively higher level of protection. But due to actual condition and ethics, attenuated cercariae vaccine can't be used directly on humans. Many speculations and explanations for the mechanisms of protection induced by attenuated cercaria focuses on two aspects: Attenuation lead to the change of cercaria components and consequently will more effectively activate the immunocytes. Another opinion is that attenuated cercariae failed to mature into worms to lay eggs and therefore avoid the downregulation and suppression on host's immune responses brought by eggs deposition and soluble egg antigen releasing, which will facilitate the effective activation of attenuated cercaria antigen-primed lymphocytes when the host's lymphoctyes encount with normal cercariae again. Previous research mainly focused on in vivo observation and analysis of effective stage of acquired immune response or comparing normal and attenuated cercaria antigen components. These results have provided supports for understanding the molecular mechanisms of protection induced by attenuated cercariae.Based on the important role of innate immunity playing in in immune initiation and regulation, to observe and compare the effect of normal and ultraviolet-attenuated cercaria antigen on antigen presenting cells (APCs) would also have important significance, which may supply new opinion for explaining the molecular mechanism of protection induced by radiation-attenuated cercariae. In one side, APCs uptake pathogen components and degrade them into small antigen peptides,which were presented by major histocompatibility complex II (MHC II) for being recognized by T cell receptor (TCR). On the other side, APCs recognize pathogen-associated molecular pattern (PAMP) through pattern recognition receptors (PRRs) and initiate signal transduction and gene expression, and secrete multiple cytokines playing important regulatory role on immune responses.This research based on the key role of APCs in initiating and regulating immune responses, focused on of MHC II expression regulation. We mainly observed the immunoregulation of two types of important antigens involving in schistosome infection on early and late stage, that is, cercaria (normal cercaria antigen, NCA; and attenuated cercaria antigen, ACA) and egg antigens, on mouse macrophages model cell line RAW 264.7. Our research showed that Schistosoma japonicum soluble egg antigen (SEA) could significantly attenuate IFN-γ-induced MHC II expression on macrophages; IFN-γcould promote SEA-induced IL-10 and IL-6 production from macrophages; IL-10 played an important role in mediating SEA-induced MHC II suppression, SEA attenuated MHC II expression also through inducing IL-6 production; In presence of IFN-γ, TGF-βproduction induced by SEA from macrophages was suppressed, and thus at least in vitro, TGF-βwas irresponsible for the suppression of MHC II expression due to SEA.Our results also demonstrated that NCA and ACA regulated MHC II expression on macrophages differently. That was, NCA could significantly attenuate IFN-γ-induced MHC II expression, but ACA showed nearly no impact on IFN-γ-induced MHC II expression in macrophages. Compared with ACA, NCA induced significantly increased IL-10, IL-6 and PGE2 production from macrophages in presence of IFN-γ. These results suggested that normal cercariae might evade immune attack through induction of suppressive cytokines to down-regulate MHC II expression. Ultraviolation might result in the change of cercaria components and abrogate or suppress the factors among them that can suppress MHC II expression and thus effectively prime and activate T lymphocytes.In conclusion, this study explored the explanation for immune downregulation and suppression of during the late stage of schistosomiasis, as well as the discrepant immune responses induced by normal cercaria infection and attenuated cercaria vaccination. The underlying molecular mechanisms related with these findings merit further study.