Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro

Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host

Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen

Alveolar echinococcosis (AE) is caused by infection with the larval stage of the tapeworm Echinococcus multilocularis. An increasing understanding of immunological events that account for the metacestode survival in human and murine AE infection prompted us to undertake explorative experiments tackling the potential of novel preventive and/or immunotherapeutic measures. In this study, the immunoprotective and immunotherapeutic ability of recombinant EmP29 antigen (rEmP29) was assessed in mice that were intraperitoneally infected with E. multilocularis metacestodes. For vaccination, three intraperitoneal injections with 20μg rEmP29 emulsified in saponin adjuvants were applied over 6 weeks. 2 weeks after the last boost, mice were infected, and at 90 days post-infection, rEmP29-vaccinated mice exhibited a median parasite weight that was reduced by 75% and 59% when compared to NaCl- or saponin-treated control mice, respectively. For immunotherapeutical application, the rEmP29 (20μg) vaccine was administered to experimentally infected mice, starting at 1 month post-infection, three times with 2 weeks intervals. Mice undergoing rEmP29 immunotherapy exhibited a median parasite load that was reduced by 53% and 49% when compared to NaCl- and saponin-treated control mice, respectively. Upon analysis of spleen cells, both, vaccination and treatment with rEmP29, resulted in low ratios of Th2/Th1 (IL-4/IFN-γ) cytokine mRNA and low levels of mRNA coding for IL-10 and IL-2. These results suggest that reduction of the immunosuppressive environment takes place in vaccinated as well as immunotreated mice, and a shift towards a Th1 type of immune response may be responsible for the observed increased restriction of parasite growth. The present study provides the first evidence that active immunotherapy may present a sustainable route for the control of AE