Immunosuppression in the definitive and intermediate hosts of the human parasite Schlistosoma mansoni by release of immunoactive neuropeptides (neuroimmunomodulation/conformational changes/neutral endopeptidase/parasite neuropeptides/host-parasite interactions)

Evidence supporting the concept that the parasitic trematode Schistosoma mansoni may escape immune reactions from its vertebrate (man) or invertebrate (the fresh- water snail Biomphalaria glabrata) hosts by using signal mol- ecules it has in common with these hosts was obtained by the following experiments. The presence of immunoactive proop- iomelanocortin (POMC)-derived peptides (corticotropin (ACTH), fi-endorphin) in, and their release from, S. mansoni was demonstrated. Coincubation of adult worms with human polymorphonuclear leukocytes or B. glabrata immunocytes led to the appearance of a-melanotropin (MSH) in the medium. The conclusion that this a-MSH resulted from conversion of the parasite ACTH by neutral endopeptidase 24.11 (NEP) present on these cells was supported by the fact that the a-MSH level in the medium was markedly reduced by addition of the specific NEP inhibitor phosphoramidon. This interpretation is substan- tiated by the fact that no conversion was observed in compa- rable tests with human monocytes, which exhibit no NEP activity. a-MSH has the capacity to inactivate formerly active immunocytes not only from the definitive host (man, hamster) but also from the intermediate host (B. glabrata), as determined by microscopic computer-assisted examination of conforma- tional changes. POMC-derived peptides have been detected in B. glabrata hemolymph 2, 10, and 24 days after infection by S. mansoni miracidia. Immunocytes from infected snails were found to be inactivated, and this inactivation was prevented by antibodies directed against ACTH and a-MSH. The immuno- active fi-endorphin released from S. mansoni does not appear to be subject to enzymatic conversion. Since it is active at lower concentrations, it may be used for distant signaling.