Regulating The Regul Ator: IL-10 Increases CD4~+ CD25~+ Regulatory T Cells While Impairs Their Immuno-regulatory Activity In Schistosoma Japonicum Infected BALB/c Mice

A number of evidence surpport that infection with helminth such as schistosome elicit protective immune response in host to recognize and eliminate the invading pathogen. However, unwanted collateral tissue immunopathological lesions result from an exuberant immune response also can occurre in parallel. In a bid to maintain or restore a homeostatic enviroment, many strategies evolves to manipulate the regulatory network in host to downregulate the immunity and minimizing severe pathology in the host. On the other hand, subversion of immunity also contributes to the evasion of helminth form immune clearance and prolongs parasite burden in the host. Moreover, helminth infection frequently shows reduced immune responses not only to the parasite itself, but also to unrelated antigens, as well as to inhibiting the efficacy of vaccine. Therefore, surviving of a given helminth infection requires the generation of a controlled immune response in the host that recognizes and eliminates the invading pathogen, limiting the collateral dame to self tissues, as well as prevents excess immunosuppression. The complicated and precise immuneregulation mechanisms underlying need to be further investigated.It is thought generally that several potential mechanisms may involve in the immune suppression including the balance between Th1/Th2 immune response, apoptosis of immunocyte, production of immunosuppressive cytokines such as IL-10, immunosuppressive CD8+Ts cells and infection induced CD4~+CD25~+Treg cells. Among these, a large body of recent studies have highlighted the importance of pathogen induced CD4+CD25+Treg cells and IL-10 in immuno-suppression in infection.Lots of studies have proven that CD4~+CD25~+Treg cells can be induced (iTreg cells) in peripheral under particular conditions of antigen exposure such as bacterial, viral, parasite antigens and prevent infection induced immunopathology but may allow the long-term pathogen survival. Evidence from other groups and our previous studies showed that Schistosome infection, their eggs and even the egg antigen derived peptides induced the generation of iTreg cells and subsequently resulted in the downregulation of the host immune response.The role of pathogen induced IL-10 as a key pleiotropic immunoregulator during infection with viruses, bacteria, protozoa, and helminths as been well documented. It is well accepted that IL-10 inhibits the activity of Th1 cells, NK cells, and macrophages, all these are required for optimal pathogen clearance but also contribute to tissue damage. In consequence of the downregulation of the immune response in host, IL-10 impedes pathogen clearance, ameliorate immunopathology. Ablation of IL-10 signaling results in the onset of severe, often fatal immunopathology in a number of infections such as T. gondii, malaria, and Trypanosoma cruz.Although the essential role of iTreg cells or IL-10 in regulating the immune response in infections has been well demonstrated, much less attention has been devoted to the potential regulatory role of IL-10 on iTreg cells. Only study more resently suggests that IL-10 signals is needed to maintain expression of the transcription factor Foxp3 and suppressive function of iTreg cells, even though relatively little data about the detailed mechanism is available. Here, in this study, we adopted S. japonicum infected mice model to address this question. By elevating the level of IL-10 with rmIL-10 i.p injection or blocking the IL-10 signals via treatment with anti-IL-10 or anti-IL-10R both in vivo and in in vitro culture systems. Our results demonstrated that IL-10 contributed to the production of iTreg cells by upregulation of serum TGF-b while impairing their immunosuppression activity by downregulation of membrane TGF-β.and probably CTLA4 and GITR on iTreg cells. These results suggested that during infection, the quantity and immunoregulatory activity of iTreg cells was fine-tuned, at least in partially mediated by IL-10, to reach an appropriate balance between immune effction and suppression, which aimed to minimize harmful immunopathology but without completely swithing off host immune responses. And our findings provide a new insight regarding the regulatory mechanism of the host immune balance, by which, the host immune response against microorganisms is precisely controlled and regulated to reach the appropriate balance which may finally favorite both host and microorganisms.