Immunosuppression in the definitive and intermediate hosts of the human parasite Schistosoma mansoni by release of immunoactive neuropeptides.
Evidence supporting the concept that the parasitic trematode Schistosoma mansoni may escape immune reactions from its vertebrate (man) or invertebrate (the freshwater snail Biomphalaria glabrata) hosts by using signal molecules it has in common with these hosts was obtained by the following experiments. The presence of immunoactive proopiomelanocortin (POMC)-derived peptides [corticotropin (ACTH), beta-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 alpha-melanotropin (MSH) in the medium. The conclusion that this alpha-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 alpha-MSH level in the medium was markedly reduced by addition of the specific NEP inhibitor phosphoramidon. This interpretation is substantiated by the fact that no conversion was observed in comparable tests with human monocytes, which exhibit no NEP activity. alpha-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 conformational 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 alpha-MSH. The immunoactive beta-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.
Duvaux-Miret
O
O
Centre d'Immunologie et de Biologie Parasitaire, Institut National de la Santé et de la Recherche Médicale Unité 167, Institut Pasteur, Lille, France.
Stefano
G B
GB
Smith
E M
EM
Dissous
C
C
Capron
A
A
D000324:Adrenocorticotropic Hormone / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001700:Biomphalaria / Q000276:immunology*; D002478:Cells, Cultured; D006224:Cricetinae; D006458:Hemolymph / Q000378:metabolism; D066298:In Vitro Techniques; D009479:Neuropeptides / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013491:Suppressor Factors, Immunologic; D000521:alpha-MSH / Q000276:immunology / Q000378:metabolism; D001615:beta-Endorphin / Q000276:immunology / Q000378:metabolism
D009479:Neuropeptides; D013491:Suppressor Factors, Immunologic; D000521:alpha-MSH; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone