Changes in IgE- and antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel

Abstract

Background: Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcepsilon receptor-bearing cells, such as mast cells and basophils, has not been investigated in relation to human immunity to schistosomes. Chemotherapy with praziquantel (PZQ) kills schistosomes living in an in vivo blood environment rich in IgE, eosinophils and basophils. This releases parasite Ags that have the potential to cross-link cell-bound IgE. However, systemic hypersensitivity reactions are not induced by treatment. Here, we describe the effects of schistosomiasis, and its treatment, on human basophil function by following changes in total cellular histamine and in vitro histamine-release induced by schistosome Ags or anti-IgE, in blood samples from infected Ugandan fishermen, who are continuously exposed to S. mansoni infection, before and 1-day and 21-days after PZQ treatment.

Results: There was a significant increase in the total cellular histamine in blood samples at 1-day post-treatment, followed by a very significant further increase by 21-days post-treatment. In vitro histamine-release induced by S. mansoni egg (SEA) or worm (SWA) Ags or anti-IgE antibody, was significantly reduced 1-day post-treatment. The degree of this reduction correlated with pre-treatment infection intensity. Twenty-1-days post-treatment, SEA-induced histamine-release was still significantly lower than at pretreatment. Histamine-release was not correlated to plasma concentrations of total or parasite-specific IgE, nor to specific IgG4 plasma concentrations.

Conclusion: The biology of human blood basophils is modulated by S. mansoni infection and praziquantel treatment. Infection intensity-dependent suppression of basophil histamine-release, histamine-dependent resistance to infection, and similarities with allergen desensitisation are discussed as possible explanations of these observations.

Figure 1

Increases in total cellular histamine content of blood from S. mansoni-infected individuals pre-treatment, 1- and 21-days post-treatment. The changes in total cellular histamine content (ng/ml) from washed blood of S. mansoni-infected individuals (n = 25) from pre-treatment levels to 1-day (black square) or 21-days (open square) after treatment with praziquantel. Any point that plots on the diagonal line is unchanged from the pre-treatment level. The differences in the levels of total cellular histamine were statistically significant between all time points and increased pre-treatment<1-day post-treatment<21-days post-treatment.

Figure 2

The percentage of histamine released from the blood of S. mansoni-infected individuals, pre- and post-treatment, after in vitro stimulation with anti-IgE or schistosome Ag. Histamine-releasability (the maximum level of histamine-release, expressed as the % of total cellular histamine content of the blood of each individual), from the washed blood cells of S. mansoni-infected individuals after in vitro stimulation with either SEA, SWA or anti-IgE. Histamine-releasability in vitro for each infected individual at the pre-treatment time point is compared with that 1-day (black square) and 21-days (open square) after treatment after in vitro stimulation with SEA (Fig 2a), SWA (Fig 2b) and anti-IgE (Fig 2c). Any point that plots on the diagonal line is unchanged from the pre-treatment level. The differences between the levels of histamine-releasability between pre-treatment and 1-day post-treatment were statistically significant for all stimuli. The differences between the levels of histamine-releasability between pre-treatment and 21-days post-treatment were statistically significant and nearly significant for SEA-stimulated and anti-IgE-stimulated histamine release, respectively.

Figure 3

Plasma levels of Ag-specific IgE and IgG4 measured at each time point in the plasma of S.-mansoni-infected people. Antibody levels measured by ELISA at pre-treatment (N = 32), 1 day post-treatment (N = 32) and 21 days post-treatment (N = 25) are expressed as OD values. Individual measurements are represented by dots. Medians are represented by horizontal bars.

Figure 4

The relationship between S. mansoni pre-treatment infection intensity and the histamine-releasability from the blood of infected individuals, pre- and post-treatment, after stimulation with anti-IgE or schistosome Ag. Histamine-relasability (the maximum level of histamine-release, expressed as the % of total cellular histamine content of the blood of each individual), from the washed blood cells of S. mansoni-infected individuals after in vitro stimulation with either SEA (n = 29), SWA (n = 32) or anti-IgE (n = 32), compared with the pre-treatment levels of S. mansoni-infection (eggs per gramme of stool, epg). Statistically significant correlations between epg and histamine-releasability are shown (Spearman's rank correlations).