Human schistosome infection and allergic sensitisation

Abstract

Several field studies have reported an inverse relationship between the prevalence of helminth infections and that of allergic sensitisation/atopy. Recent studies show that immune responses induced by helminth parasites are, to an extent, comparable to allergic sensitisation. However, helminth products induce regulatory responses capable of inhibiting not only antiparasite immune responses, but also allergic sensitisation. The relative effects of this immunomodulation on the development of protective schistosome-specific responses in humans has yet to be demonstrated at population level, and the clinical significance of immunomodulation of allergic disease is still controversial. Nonetheless, similarities in immune responses against helminths and allergens pose interesting mechanistic and evolutionary questions. This paper examines the epidemiology, biology and immunology of allergic sensitisation/atopy, and schistosome infection in human populations.

Figure 1

Possible regulatory mechanisms in helminth infections. Primary response (a) to parasite antigens involves Th2 polarization, IgE production, and eosinophil, mast cell, and basophil activation (I), mechanisms similar to those observed in allergic sensitisation (c). This Th2-response may be induced by parasite-secreted antigens such as the Omega-1 secreted by S. mansoni eggs [25]. However, with increasing parasite load or chronic infection (b), regulatory B cells are activated which suppress Th2 responses (II) via IL-10 secretion or CD23 expression [26], and/or contribute to the recruitment of Tregs [27]. Tregs (III), which may also be induced and expanded by parasite antigens [28, 29], either induce anergic Th2 cells (expressing GITR and CTLA4) unable to progress through to effector cells, or modify downstream effector functions such as B cell switch to IgG4 and/or alternative activation of macrophages, resulting in immunological tolerance (reviewed by [30]). This immunosuppression is induced in the context of helminth infection, but may also expand to allergen-induced inflammation (gray line), hence suppressing allergy. DC: dendritic cell; B: B cell, Eos: eosinophil; Bas: basophil; MC: mast cell; GITR: glucocorticoid-induced TNFα-related protein; CTLA4: cytotoxic T lymphocyte antigen 4; AAM: alternatively activated macrophage; Breg: regulatory B cell; Treg: regulatory T cell. The question mark (?) denotes lack of strong evidence. Figure adapted from [30, 31] and collated information from the cited references.

Figure 2

Interaction between CD23 and its ligands, IgE and CD21. Binding of IgE stabilises membrane-bound CD23 and inhibits IgE synthesis (I) from activated B cells while in the absence of IgE binding the CD23 is cleaved by ADAM10 (a disintegrin and metalloprotease protein 10) and this destabilisation enhances IgE synthesis (II). However, soluble CD23 (sCD23) fragments resulting from the cleavage have the ability to bind IgE with different affinities depending on their oligomerization state: trimers (III) bind IgE with high affinity while monomers (IV) bind with low affinity. Trimers enhance IgE synthesis by their ability to also bind CD21 receptor (III) while monomers fail to bind CD21 and inhibit IgE synthesis (IV) (adapted from [–36]).