Worms: Pernicious parasites or allies against allergies?

Abstract

Type 2 immune responses are most commonly associated with allergy and helminth parasite infections. Since the discovery of Th1 and Th2 immune responses more than 30 years ago, models of both allergic disease and helminth infections have been useful in characterizing the development, effector mechanisms and pathological consequences of type 2 immune responses. The observation that some helminth infections negatively correlate with allergic and inflammatory disease led to a large field of research into parasite immunomodulation. However, it is worth noting that helminth parasites are not always benign infections, and that helminth immunomodulation can have stimulatory as well as suppressive effects on allergic responses. In this review, we will discuss how parasitic infections change host responses, the consequences for bystander immunity and how this interaction influences clinical symptoms of allergy.

Figure 1

Helminth infections are associated with both promoting and reducing allergic symptoms. Helminths interact strongly with the host immune system, but the type of response is heavily influenced by the chronicity of infection, the species involved and/or worm burden, ultimately tipping the balance towards more detrimental and type 2 response or beneficial and regulatory responses. Subsequently, this balance is further influenced by cofactors such as host genetics, socioeconomic status, coinfections and the composition and diversity of the microbiome leading to the development of clinical symptoms and allergies or tolerance in the host. Image is adapted from Servier Medical ART

Figure 2

Immune responses during helminth infections. Depending on their life cycle, various helminth species will pass or reside in (the proximity of) the lung and the gut. Consequently, damage will occur, leading to the release of alarmin cytokines IL‐33, IL‐25 and thymic stromal lymphopoietin (TSLP) by epithelial cells and tuft cells (gut). These cytokines will act on innate lymphoid cells (ILC)2 and on dendritic cells (DCs), which will migrate to the draining lymph node and skew naïve T cells towards polarized Th2 cells, producing the cytokines IL‐4, IL‐5 and IL‐13, in a similar fashion as ILC2s. These cytokines are central to the type 2 immune response and drive the isotype switch to IgE immunoglobulins, act on eosinophils, mast cells and drive the development of alternatively activated macrophages. All these elements are instrumental in worm expulsion but can also promote tissue damage, anaphylaxis and allergic responses towards bystander antigens. These responses are balanced by various cells from the regulatory network: for example regulatory T and B cells, regulatory macrophages and tolerogenic DCs. These regulatory cells can act on other cell types directly or through the production of anti‐inflammatory cytokines IL‐10 and TGF‐β, as well as by the induction of anti‐inflammatory IgG4, leading to immune tolerance and damage control, but at the same time prevent worm expulsion, promoting chronic helminth infections. Image is adapted from Servier Medical ART