Trichinella spiralis Excretory-Secretory Products Stimulate Host Regulatory T Cell Differentiation through Activating Dendritic Cells

Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory-secretory (ES) products, characterized by increase of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) Treg cells accompanied by high levels of IL-10 and TGF-beta. T. spiralis adult worm excretory-secretory products (AES) and muscle larvae excretory-secretory products (MES) were both able to activate BMDCs in vitro to facilitate their maturation and to create regulatory cytokines IL-10 and TGF-beta. The T. spiralis AES- and MES-pulsed dendritic cells (DCs) possessed abilities not only to present antigens to sensitized CD4(+) T cell to stimulate their proliferation but also to induce naive CD4(+) T cells to differentiate to Treg cells secreting IL-10 and TGF-beta. The passive transfer of T. spiralis AES- and MES-pulsed bone marrow-derived dendritic cells (BMDCs) conferred the naive mice to acquire the differentiation of Treg cells. T. spiralis AES possesses a better ability to induce Treg cells than did MES, although the latter has the ability to induce CD4(+)CD25(-)Foxp3(+) Treg cells. The results obtained in this study suggested that T. spiralis ES products stimulate the differentiation of host Treg cells possibly through activating dendritic cells to create a regulatory environment that benefits the survival of the parasite in the host.