Schistosomes and eosinophils

Study of the interaction between schistosomes and eosinophils was the first step leading to the description of in vitro eosinophil-mediated cytotoxicity against parasitic targets and to the role of this polymorphonuclear leucocyte in immunity to helminths. Elegant studies have been initiated by Butterworth's group, evidencing for the first time the human IgG antibody-eosinophil co-operation responsible for the killing of Schistosoma mansoni schistosomula and approaching more recently the molecular basis of this mechanism. Similar studies on experimental models, mainly performed in the rat, have allowed a better understanding of the immune mechanisms leading to activation and regulation of eosinophil effector function. The necessary requirement for rat mast cell-eosinophil interaction in schistosomula killing was shown to depend on mast cell soluble mediators among which the eosinophil chemotactic factor of anaphylaxis (ECF-A) played a significant role in increasing both IgG-mediated eosinophil cytotoxicity and the expression of IgG-Fc receptors on rat eosinophils as detected by EA-rosette assay. The characterization of immunoglobulin classes involved in rat eosinophil cytotoxicity revealed the preferential participation of anaphylactic antibodies. Whereas IgG2a antibodies were required early after infection, an exclusive role could be attributed to IgE antibodies at a later phase of rat schistosomiasis. The participation of IgE antibodies in this new system of eosinophil cytotoxicity was very precisely demonstrated by immunoadsorption and inhibition studies. Moreover, a specific receptor for IgE was identified both on rat and on human eosinophils, using a rosette assay with IgE myeloma protein coated erythrocytes. Several mechanisms accounting for immunoregulation of rat eosinophil cytotoxicity are proposed. They involve the presence of immune complexes, the possible interaction with the IgE-macrophage system and the inhibitory role of a schistosome derived inhibitory factor (SDIF) on mast cells. The numerous studies performed in this schistosome-eosinophil model have led to the concept that besides the in vitro and in vivo effector function of eosinophils, anaphy lactic antibodies and their binding capacity to cell receptors take an important part in the expression of immunity.