Regulatory Function Of P.Yoelii Derived Recombinant MIF On Immune System In Mouse

Malaria continues to be one of the most severely infectious diseases in the world, still with216million clinical cases reported and0.65million of deaths in2010. It not only theatens the health and life quality in epidemic areas, but also damages the economy and society in developing countries. During the longtime battle with malaria, thoroughly known the biology of this parasite is a critical point. Similar to other infectious disease, malaria needs the host immune system to control and eliminate. However, the parasite escaping of being attacked by the host immune system through its immunosuppression function or causing a strong pro-inflammatory response in cerebral malaria, is its main feature. But now, little is known about in which exact ways the parasite regulates the host immune system.A multifunctional cytokine Macrophage Migration Inhibitory Factor (MIF) takes part in many infectious and immune related disease, also have important role in malaria pathology and especially in anemia symptoms. There are four reported plasmodium derived MIF (pMIF):Plasmodium falciparum MIF (P/MIF), P.vivax MIF (PvMIF), P.berghei MIF(P6MIF) and P.yoelii MIF (PyMIF). It is proved that the senior structure of pMIF and MIF is highly conserved. There are many research teams devote their efforts to research the function of pMIF, but no definite conclusion has been reached about its exact role in immune system. And it has been proved that macrophage is one of its target cells in vitro, which points out that pMIF could regulate the host immune system. In this study, we analyze the function of PyMIF in vitro and in vivo separately to detect its possible target cells in host immune system.Dendritic cells with the capacity to activate naive T cells are the most potent APC in immune systems and play an important role in immune protection against malaria. In previous research, we found that PyMIF could down-regulate TLR4expression of DC in vitro. After co-colutured with PyMIF treated DC, the CD69expression of CD8+T decreased. And then my work focus on the function of PyMIF on bone marrow derived dendritic cell (BM-DC)、CD4+T cells and splenocyte. We found that PyMIF didn’t directly regulate BM-DC’s function on IL-10secreting、activation of CD4+T cells or differentiation of splenocyte in vitro:PyMIF have no influence on IL-10secreting of BM-DC; After co-cultured with PyMIF treated BM-DC, the CD69expression and IL-2secreting of CD4+T cells did not change. And PyMIF either couldn’t influence the CD69expression and IL-2secreting of CD4+T cells directly. PyMIF didn’t change differentiation of splenocyte to Th1or regulatory T cells (Treg).In order to simulate the action modes of PyMIF on infectious condition in vivo, we construct four infectious modes including lethal P.yoelii17XL parasites infected BALB/c or DBA/2mice, and nonlethal P.yoelii17XNL parasites infected BALB/c or DBA/2mice, and then intravenously injected with recombinant PyMIF on early or late infectious stages. The results showed that PyMIF decreased the parasitemia in all four infectious conditions, but regulated different immune cells in different modes. In the lethal P.yoelii17XL infected BALB/c mice modes, PyMIF down-regulated the proportion of both mDC and pDC, and up-regulated the proportion of T-bet+IFN-γ+cells in CD4+T cells. In the lethal P.yoelii17XL infected DBA/2mice modes, PyMIF down-regulated the proportion of macrophage. However, PyMIF didn’t change the proportion of cells detected in the nonlethal P.yoelii17XNL infected BALB/c and DBA/2mice modes. In the four modes, the IFN-γ in splenocyte supernatants had a obvious trend of increase after intravenously injected with recombinant PyMIF. In addition, we found a dramatically increase of parasitemia and a significant decreased of serum blood IFN-y of mice infected with lethal P.yoelii17XL PyMIF knock out parasites by comparison with the wide type ones. Our data have great significance to the research on PyMIF function, and mechanisms about which immune cells or cytokine take part in the regulation by PyMIF in the knock out parasites infectious modes is under investigation.