Susceptibility and immunity to helminth parasites

Abstract

Parasitic helminth infection remains a global health problem, whilst the ability of worms to manipulate and dampen the host immune system is attracting interest in the fields of allergy and autoimmunity. Much progress has been made in the last two years in determining the cells and cytokines involved in induction of Type 2 immunity, which is generally protective against helminth infection. Innate cells respond to 'alarmin' cytokines (IL-25, IL-33, TSLP) by producing IL-4, IL-5 and IL-13, and this sets the stage for a more potent subsequent adaptive Th2 response. CD4+ Th2 cells then drive a suite of type 2 anti-parasite mechanisms, including class-switched antibodies, activated leukocytes and innate defence molecules; the concerted effects of these multiple pathways disable, degrade and dislodge parasites, leading to their destruction or expulsion.

Figure 1

Innate and adaptive immune mechanisms in helminth infections in the lung and gut. In the lung, traversing parasites elicit epithelial cell alarmin production (IL-25 and IL-33, the latter requiring preceding expression of TFF-2) that activate innate cells including innate lymphoid cells, eosinophils and DCs; DC stimulation of helminth-specific Th2 results in amplified production of IL-4, IL-5 and IL-13 that drive alternative activation of macrophages and considerable expansion of eosinophils, implicated in immune attack on migrating helminth larvae. In the intestine, similar innate triggers (including TSLP) generate innate and adaptive populations, including mast cells and basophils, and act on intestinal epithelial cells to induce goblet cell differentiation and expression of molecules inimical to parasite persistence. Adaptive Th2 response promotes B cell production of protective antibodies.

Figure 2

Two models of immunoregulation in helminth infection are H. polygyrus and L. sigmodontis. In H. polygyrus, infection suppresses mast cell hyperplasia and modulates DC responsiveness to TLR ligation; in addition both Tregs and Bregs are generated and Th2 responses suppressed. As well as parasite-specific immunity, bystander responses to allergens and autoantigens are also suppressed. In L. sigmodontis, it is thought that natural T regs expand early in infection, followed by a later wave of adaptive Tregs; these populations induce anergy in effector T cells, impairing both parasite immunity and allergic responses to third-party allergens [5].