Abstract
BackgroundThe rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a Schistosoma haematobium endemic area and further investigated the relationship between the cytokine responses and infection intensity.MethodsSchistosome adult worm antigen-specific IFN-γ, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to S. haematobium infection (aged 6 to 40 years old). The cytokines were measured using capture ELISAs and the data thus obtained together with S. haematobium egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches.ResultsAge profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11–12 years) followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine) while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-γ followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-γ did not show a significant relationship with infection status or intensity and were positively associated with each other.ConclusionTaken together, these results show that the IL-10 responses develop early compared to the IL-5 response and may be down-modulating immunopathological responses that occur during the early phase of infection. The results further support current suggestions that the Th1/Th2 dichotomy does not sufficiently explain susceptibility or resistance to schistosome infection.
Highlights
The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts
Given that differences occur in the immunology and immunopathology of murine and human schistosomiasis [16,17], human studies are essential for a clearer definition of human schistosome immuno-epidemiology
We have previously compared the same cytokine response across populations exposed to different infection intensities and showed that the rate of development of S. haematobium-specific cytokine responses was affected by the host's history of infection, with responses developing earlier in areas of high infection intensity compared to areas of low infection intensity [48]
Summary
The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. Schistosome immuno-epidemiology studies have shown that the development of antigen-specific immune responses is related to cumulative exposure to parasite antigens [8,9] and that the rate of development of different components of these responses give distinct profiles across the host age range [10]. These profiles have facilitated the identification of responses associated with protection to infection/re-infection. Given that differences occur in the immunology and immunopathology of murine and human schistosomiasis [16,17], human studies are essential for a clearer definition of human schistosome immuno-epidemiology
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