Species-related innate resistance to Schistosoma mansoni. Role of mononuclear phagocytes in schistosomula killing in vitro.

Abstract

Resistance to infection with the multicellular parasite Schistosoma mansoni has been previously demonstrated to vary among several host species. The current investigation was designed to examine the basis for this species-related resistance in vitro. Adherent peritoneal macrophages or peripheral blood mononuclear cells from several species of host animals were incubated with S. mansoni schistosomula for 18-24 h; parasite viability was then assayed by methylene blue exclusion. Peritoneal exudate macrophages from susceptible species, such as mice (C57Bl/6) and hamsters killed, respectively, 6.6 +/- 2 and 8.0 +/- 2% of incubated schistosomula. In contrast, cells from resistant species: rats, guinea pigs, and rabbits, killed 21 +/- 2.3, 15 +/- 4.6, and 17 +/- 5.5%, respectively. Furthermore, blood monocytes from rabbits resulted in a mean of 25.9 +/- 2.8% dead organisms. Schistosomula killing by mononuclear phagocytes obtained from resistant species (rats or rabbits) was dependent on the cell/parasite ratio. Significant schistosomula mortality resulted from culture supernatants of rat macrophages or rabbit monocytes. Killing by cells from both species was significantly reduced upon addition of L-arginine, while catalase reduced killing only by rat macrophages. We conclude that mononuclear phagocytes may play a key role in species-related innate resistance to schistosomiasis; their in vitro schistosomulicidal activity parallels the known in vivo susceptibility of the donor species. Killing is mediated by lysosomal enzymes (arginase) and by products of oxidative metabolism, the predominant mechanism depends on the specific animal species.