Immunity to Schistosomiasis: Role of Eosinophils in parasite killing and in tissue injury

Abstract

Eosinophilia is associated with helminth infections and or allergic conditions. However, the precise role of this cell • has, until recently, been speculative. There is accumulating evidence to suggest that eosinophils may be involved in the expression of immunity to parasites; On the other hand eosinophils have been implicated in various allergic and inflammatory conditions. If eosinophil dependent immune mechanisms were, for example, to be incorporated into the desiqn of a schistosome vaccine, it is imperative that there is does not result in adverse reactions. This study has thus set out to examine the relationship between eosinophil levels, immune mediators, and the ability to kill schistosomula of Schistosoma metisoni in vitro, in patients treated for S. menson: in fections. The potential role of eosinophils III inflammatory responses has been studied by assesing their ability to adhere and cause damaqe, to cultured human " umbilical vein endothelial cells (E.C.). Patients for the study were recruited from outpatient clinics after a positive diagnosis for S. mansoni infections or for mild allergic eosin oph il ia. Celis were pu r ifi ed on discontinous metrizamide gradients to yield highly enriched fractions of mon onucle ar cells, neutr oph ils, and eosin ophils. Serurn samples were retained to assay for antibodies to crude parasite antigens. Antibody dependent schistosomula killing was estimated by visual microscopy; Anti-parasite antibodies, and cytokines were measured by elisa; Adherence and damage to endothelial cells by isotope uptake and release assays. The results indicated that eosinophil levels were significantly increased in patients treated for S. manson; infections. In group 1, patient's peripheral blood eosinophil counts rose from a mean of 17 5/ul before treatment. to 745/ul at 3 weeks following treatment, and in group 2 from 181 lul to 1066/ul. The increase in eosinophil levels was positively correlated with a rise in circulating anti-adult worm antibodies (r = 0.587, P <0.05). Despite some enhanced eosinophil helminthotoxicity following treatment in some of the individuals In group 1 (7/15), the change overall was not significant. In group 2, in which a different standard anti-schistosomular antibody was used, the eosinophil killing capacity recorded at 3 weeks was lower than that before commencement of treatment (t = 2.89, P <0.01). The eosinophil stimulating activity, detected in cultured mononuclear cells supernatants (MCS) from individual patients correlated with eosinophil levels (r = 0.582, P <0.02). IL-5 levels in MCS were correlated with anti-egg antibodies (r = 2.294 P < 0.05). These results . indicate that peripheral-blood eosinophils are increased following treatment, but their ability to kill schistosome larvae is variable and may depend on other cell activating factors; The results also suggest that egg antigens may be important In the induction of IL-5, in schistosome infections.