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  • Review Article
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The immunobiology of schistosomiasis

Key Points

  • Schistosome worms are complex multicellular parasites that cause chronic disease in millions of people.

  • Schistosomes induce a dominant, distinct, polarized T helper 2 (TH2)-cell response that is intimately involved in the development of many of the pathological changes that accompany infection, but which also allows host survival while infected.

  • The parasites can persist for many years in the immunocompetent host. However, infected individuals can develop resistance to superinfection.

  • Although schistosomes typically induce a pronounced TH2 response, it is the development of a balanced TH response that is most important to prevent disease progression; both TH1 and TH2 components, if excessive, can lead to damaging pathology.

  • Host-derived signals can provide cues to guide schistosome development, and proteins have been identified in the parasite surface membrane that could act as receptors for such signals.

  • Schistosome infection might influence the development of immune responses and disease that are caused by concurrent infections with other pathogens, autoimmune disease and allergy.

  • The TH2 response to schistosomes is initiated by the egg stage of the parasite, and carbohydrates on egg antigens are thought to be integral to this process.

  • Dendritic cells that are exposed to schistosome egg antigens are not activated in a conventional manner, but they are able to potently induce TH2 responses.

  • Reflecting the complexity of the host–parasite relationship and underscoring the need to more fully understand both immune-response development and parasite biology, an effective rationally designed anti-schistosome vaccine has yet to be produced.

Abstract

Schistosomes are parasitic worms that are a prime example of a complex multicellular pathogen that flourishes in the human host despite the development of a pronounced immune response. Understanding how the immune system deals with such pathogens is a daunting challenge. The past decade has seen the use of a wide range of new approaches to determine the nature and function of the immune response to schistosomes. Here, we attempt to summarize advances in our understanding of the immunology of schistosomiasis, with the bulk of the review reflecting the experimental focus on Schistosoma mansoni infection in mice.

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Figure 1: Development of the immune response in infection.
Figure 2: IL-13 and IFN-γ/IL-12 counter-regulate macrophage-activation status and control fibrosis.
Figure 3: TH2-response induction by schistosome egg antigens.

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Acknowledgements

E.J.P. is a Burroughs Wellcome Fund Scholar in Molecular Parasitology, and is supported by grants from the National Institutes of Health. A.S.M. is a recipient of a Wellcome Trust Prize Travelling Fellowship. We apologize to those authors whose work we were unable to cite owing to space limitations.

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Correspondence to Edward J. Pearce.

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DATABASES

Entrez

HBV

HCV

HIV-1

Mycobacterium bovis

Schistosoma japonicum

Schistosoma mansoni

Toxoplasma gondii

LocusLink

B7RP1

CD40

CD80

CD86

CD154

FcɛR1

ICOS

IFN-γ

Ifnγ

IFN-γR1

IL-1

Il4

Il4rα

IL-5

IL-6

IL-7

Il7

IL-10

Il10

IL-12

Il12

IL-13

Il13

IL-13Rα2

iNOS

MYD88

OX40

OX40L

Rag

SM1

SM2

STAT6

T1/ST2

TGF-β

TLRs

TNF

TNFRI

TNFRII

FURTHER INFORMATION

The WHO — Schistosomiasis (Bilharzia)

The WHO/UNDP/World Bank Schistosoma Genome Network

University of Cambridge Schistosomiasis Research Group

Glossary

DIGENETIC TREMATODE

Digenetic trematodes, or flukes, are extremely successful parasitic worms, the life cycle of which requires development in at least two hosts. Importantly, they can parasitize all classes of vertebrate, causing widespread medical and economic problems.

T HELPER 1/T HELPER 2

(TH1/TH2). Subsets of CD4+ T cells that are characterized by their cytokine-production profiles. TH1 cells primarily produce IFN-γ, and generally provide protection against intracellular pathogens, whereas TH2 cells mainly produce IL-4, IL-5 and IL-13, and are important for immunity to helminth parasites.

SEGREGATION ANALYSIS

This technique is used to predict the probability that certain individuals will be of a certain genotype given information about the genotypes of ancestors and assumptions about the mode of inheritance. It can be used to distinguish between different models of inheritance (for example, major gene versus multifactorial).

IDIOTYPIC REGULATION

The antigen-binding site of an antibody is an idiotype. As an immune response develops and clonal B-cell expansion occurs, the prevalence of this previously rare idiotype increases and can lead to the development of an anti-idiotypic T- and B-cell response. Focus on this once popular area of immunology is now minimal.

SEVERE COMBINED IMMUNODEFICIENCY

(SCID). A condition in which T-cell responses and antibody production are virtually non-existent, which can be caused by several immunological defects. In mice, this condition is caused by the scid mutation.

NUDE

A mutation in mice that causes both hairlessness and defective formation of the thymus, which results in a lack of mature T cells.

RAG

Recombinase activating genes (Rag1 and Rag2) are expressed in developing lymphocytes. Mice that are deficient for either of these genes fail to produce B or T cells owing to a developmental block in the gene rearrangement that is necessary for receptor expression.

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Pearce, E., MacDonald, A. The immunobiology of schistosomiasis. Nat Rev Immunol 2, 499–511 (2002). https://doi.org/10.1038/nri843

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