Immunology of hepatosplenic schistosomiasis mansoni: a human perspective

Schistosomes are multicellular eukaryote parasites that can live for many years in their mammalian host's blood, coated in host antigens, and apparently unaffected by host im mu ne effector mechanisms. The control of infection and disease caused by these organisms presents the human immune system with problems, at least superficially, more akin to those presented by tumours than those presented by viral and bacterial pathogens. However, tumours, unlike schistosomes, have not coevolved with man to live, thrive, and reproduce in their host immune environment and to optimise their continued transmission to new hosts. We can get some feel for the degree of this evolutionary adaptation from the fact that not only do schistosomes have a bewildering array of immune evasion strategies, but the continued life cycle of the parasite is dependent on the host's immune response to antigens actively secreted by the parasite egg to facilitate the passage of the egg from the blood stream to the outside world. It is reasonable to consider that such a successful and beautifully adapted parasite must be in a state of near equilibrium with its natural human host, ensuring a widespread distribution (infecting some 200 million people worldwide), but causing severe disease in a relatively small proportion of the infected population (less than 10% of the infected population in the case of hepatosplenic schistosomiasis mansoni). Equally, we must expect that immunological relationships between man and schistosomes will be intimate and complex. We are beginning to understand some aspects of these complex relationships because of excellent murine models that are currently providing many insights into not only the interactions between schistosomes and their mammalian hosts, but the way that the immune system reacts and regulates itself under chronic antigen stimulation. Extrapolations from such mouse models suggest that the severest form of human schistosomiasis mansoni, hepatosplenic disease, is caused by chronic exposure to parasite eggs lodged in liver tissues inducing, in a minority of infected individuals, immunopathological granulomatous responses and fibrosis. Other contributions to this Forum will detail the murine granulomatous cellular response to the egg and what it tells us about the cross-regulating functions of multiple cell types, cytokines, monokines, adhesion molecules, and even antibodies. The knowledge we have of specifically human responses to schistosomes falls far short of what we know of the mouse model. However, schistosomes are important human pathogens and it this that provided the initial imperative for immunological studies of these organisms. Therefore, it is important to also ask: how do results obtained from the mouse relate to those from human studies, and how much of what we have learnt so far from murine models can be related to the immunological control of hepatosplenic schistosomiasis in man! Our contribution to this Forum outlines the factors that may affect human hepatosplenic disease. We hope that this will be useful in juxtaposition to the contributions of others that are more focussed on detailed immune mechanisms and thus, necessarily, concerned more with experimental models.