Cytokine-mediated host responses during schistosome infections; walking the fine line between immunological control...

Most helminth infections of humans and animals induce similar immune responses, which are characterised by the production of Th2-associated cytokines (interleukin (IL)-4, IL-5, IL-9, IL-10, IL-13) and antibodies (IgG1--mouse, IgG4--man, IgE--both). This type-2-biased immune phenotype generally persists for the duration of the infection. Although similar types of immune responses are also triggered during allergy, atopy and anaphylaxis, chronic helminth-induced type-2-associated responses are usually held in check by appropriately regulated control mechanisms that limit the destructive potential of prolonged cytokine bias. Among numerous reported activities, helminth-induced type-2-associated immune responses have been linked to the expulsion of gastrointestinal nematodes and the formation of circumoval granulomas during schistosomiasis. However, what happens when this highly regulated, and often beneficial, type-2 immune response becomes chronic, improperly controlled, or exaggerated during helminth infections? Using schistosomiasis as a model disease, we describe the lethal consequences of inappropriate immune response induction by reviewing the literature generated from experimental animal studies and human epidemiological investigations. Development of severe and non-overlapping immunopathological phenotypes will be discussed in the context of immune deviation and in the setting of chronic and/or hyper-polarised cytokine environments.