Killing of Schistosomula of Schistosoma mansoni by Normal Human Monocytes

All mammalian species exhibit some degree of innate resistance to infection with the helminth Schistosoma mansoni. This is manifest experimentally by the discrepancy between the number of infecting cercariae and the resulting mature worm load (1). Even in the most susceptible species, such as the hamster and mouse, no more than 40 to 60% of infecting organisms develop into adult worms (2). In vitro systems have been used to elucidate potential mechanisms of schistosomula killing (3–8). However, the recognized mechanisms all are predicated upon prior schistosomiasis with the development of specific antibodies (3, 4), the availability of eosinophils (5–7), or activation of macrophages (8). The current studies were designed to evaluate possible contributions of circulatory leukocytes to naturally occurring resistance to schistosomiasis. They show that cells derived from circulatory human monocytes can kill schistosomula independent of specific antibody and complement (C). Materials and Methods. Cell preparations. Human peripheral blood mononuclear cells (PBMC) were obtained by Ficoll-Hypaque sedimentation of heparinized venous blood from normal volunteers (9). Adherent cell monolayers were prepared by two sequential incubations of 2.5 × 106 PBMC in 0.5 ml of RPMI 1640 (Kansas City Biologicals, Lenexa, Mo.) supplemented with 10% autologous plasma in Linbro tissue culture plate wells (diameter = 1.6 cm, Linbro Scientific, Hamden, Conn.) for 1 hr at 37°C. The wells were washed to remove nonadherent cells after each incubation. The dense monolayers prepared in this fashion (2.0 to 6.0 × 105 cells/well) contained 90 to 95% esterase-positive cells (10) or monocytes, 5 to 10% surface immunoglobulinbearing or B lymphocytes, 1 to 2% sheep erythrocyte-rosetting or T lymphocytes and <1% neutrophils. Neutrophil-enriched populations were prepared by dextran sedimentation of those cells pelleting during the Ficoll-Hypaque separation and consisted of over 98% neutrophils. A nonadherent, lymphocyteenriched preparation was obtained by sequential depletion of adherent cells from PBMC on two Petri dishes; it contained <1% monocytes.