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Immunopathology of schistosomiasis: a cautionary tale of mice and men

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Abstract

Murine experimental models have been used extensively to demonstrate that the specific dominance of a type 1 or type 2 cytokine response will influence the outcome of infection with a number of pathogens. Here, using a human helminth infection as an example, Padraic Fallon illustrates the problems of extrapolating from mouse to humans with respect to cytokine-associated immunopathology.

Section snippets

Type 1/type 2 cytokine responses

The T helper 1 (Th1)/Th2 dichotomy was first shown in murine CD4+ T-cell clones, which could be differentiated in terms of the cytokines they secrete: Th1 subsets produce interleukin 2 (IL-2), interferon γ (IFN-γ) and tumour necrosis factor (TNF); Th2 subsets produce IL-4, IL-5, IL-6, IL-10 and IL-13 (Ref. 4). Central to the concept of Th1- and Th2-subset responses is the tendency for the response to become polarized1. Thus, a Th1 or Th2 phenotype will ultimately dominate a response by both

Schistosome pathology in mice and humans

In areas endemic for intestinal schistosomes, most infections are relatively asymptomatic or have restricted morbidity associated with intestinal inflammation and fibrosis. However, a minority of infected individuals develop severe hepatosplenic schistosomiasis (HS) characterized by hepatic fibrosis, hepatosplenomegaly and portal hypertension. The hepatomegaly is caused by portal tract fibrosis (known as Symmers' pipe-stem fibrosis), whereas the accompanying splenomegaly is associated with

Is schistosome pathology type 1 or type 2?

It is undisputed that the schistosome egg is the principal cause of pathology in mice. Similarly, it is clear that the egg is inherently a major stimulator of type 2 cytokines in mice. As shown in Fig. 2, these two disparate observations from murine studies have been generally interpreted to give the impression that egg-driven type 2 cytokine responses are the cause of pathology in schistosomiasis. The hypothesis of type 2 cytokines causing pathology in schistosome infection has led to the

Concluding remarks

Current understanding of the immunological basis of many disease processes has been initially elucidated using murine models. This article discusses possible differences between immunological data obtained from schistosome-infected mice and humans, and is applicable to studies on many pathogens or disease processes. Experimental infection of mice in a controlled environment is somewhat removed from the multi-factorial natural infection of human populations (Table 1). Although the mouse will

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Acknowledgements

I am grateful to various colleagues, in particular D. Dunne and A. McKenzie, for critical reading of the manuscript. A. Fulford is thanked for advice on statistical analysis. P.G.F. is supported by a Wellcome Trust Career Development Award and the Medical Research Council.

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