A Taenia solium metacestode factor nonspecifically inhibits cytokine production.

Studies of the immune response in chronic helminth infections suggest that parasites modulate the host's immune response. Taenia solium metacestodes, in particular, produce molecules that down-regulate cell-mediated immunity. We have described a small RNA peptide termed metacestode factor (MF) that depresses the murine immune response to Salmonella typhimurium antigens. MF inhibits mitogen-induced proliferation, humoral and cellular responses to metacestode antigens, and inflammation surrounding metacestodes implanted subcutaneously in mice. To assess the effects of MF on cytokine production we stimulated murine spleen cells in vitro with concanavalin A and measured cytokine concentrations in the culture supernatants by enzyme-linked immunosorbent assay. When cultured with MF, the cells showed significantly decreased production of interleukin 2 (IL-2), interferon-gamma (IFN-gamma), and IL-4 as compared with mitogen alone. Exogenous rIL-2 and rIL-4 largely restored the proliferative response (85% and 71% of control cells, respectively). MF also decreased production of tumor necrosis factor-alpha (TNF-alpha) by macrophages stimulated with lipopolysaccharide and IFN-gamma. The TNF-alpha concentration was inversely correlated with the MF concentration. Experiments using spleen cells from mice treated with MF also showed a significant reduction in IL-4 concentration. These results suggest that MF inhibits cytokine production without regard to cell type or cytokine. This may explain the function of this molecule as an inhibitor of the host inflammatory and immune responses.

Field trial for reducing porcine Taenia solium cysticercosis in Mexico by systematic vaccination of pigs.

It has previously been demonstrated that immunization of pigs with a crude extract of Taenia solium metacestodes can confer a high level of protection against an egg challenge. Furthermore, vaccination of infected animals also induces an immune response against the larvae, which are either destroyed or rendered non-infectious. To assess the efficacy of immunization as a strategy for reducing the prevalence of porcine cysticercosis, a field trial of this vaccine was performed in an endemic area in the northern region of the Guerrero State, Mexico, Random samples of pigs belonging to 17 villages were examined for metacestodes by inspection of their tongues. Each animal was immunized with a dose of 150 micrograms of protein (antigenic extract from Taenia solium metacestodes) by the intramuscular route. A prevalence of 2.4% of porcine cysticercosis on average was found in these villages at the beginning of the trial (62 cysticercotic pigs out of 2650 inspected). Six of these villages were selected for the periodic vaccination of new random samples of pigs. A statistically significant decline in the prevalence of porcine cysticercosis was observed at the end of the trial, decreasing from 2.4% at the beginning of vaccination to 0.45% at the end of the trial. A reduction of 82% was observed in spite of the poor living conditions in these villages. These results are consistent with previous data and suggest that it may be possible to turn a susceptible pig population into a protected one by systematic vaccination.

Suppression of murine lymphocyte proliferation induced by a small RNA purified from the Taenia solium metacestode.

A substance from Taenia solium metacestodes that decreases lymphocyte proliferation induced by concanavalin A was isolated. The molecular weight of this substance was estimated to be slightly more than 1,450 Da. Crude metacestode factor was fractionated through a Bio-gel P-6 column. Peak 1 showed suppressive activity. After incubation with RNase the substance lost its activity. Incubation of this material with trypsin or papain increased its suppressive activity. It was stable at boiling temperature for 10 min. The incubation of this substance with murine macrophages had no effect on [3H]-thymidine uptake by cocultured fresh splenic lymphocytes stimulated with concanavalin A. Conversely, cocultures of lymphocytes pretreated with the substance and fresh splenic lymphocytes showed a decreased incorporation of [3H]-thymidine. These results suggest that this substance is a RNA-peptide molecule whose RNA moiety accounts for its suppressive activity. The findings also suggest that in vivo the factor may be a modulator of the immune response.