What Can Parasites Tell Us About the Pathogenesis and Treatment of Asthma and Allergic Diseases

Abstract

The same mechanisms that enable host defense against helminths also drive allergic inflammation. This suggests that pathomechanisms of allergic diseases represent evolutionary old responses against helminth parasites and that studying antihelminth immunity may provide insights into pathomechanisms of asthma. However, helminths have developed an intricate array of immunoregulatory mechanisms to modulate type 2 immune mechanisms. This has led to the hypothesis that the lack of helminth infection may contribute to the rise in allergic sensitization in modern societies. Indeed, the anti-inflammatory potential of helminth (worm) parasites and their products in allergy and asthma has been recognized for decades. As helminth infections bring about multiple undesired effects including an increased susceptibility to other infections, intended helminth infection is not a feasible approach to broadly prevent or treat allergic asthma. Thus, the development of new helminth-based biopharmaceutics may represent a safer approach of harnessing type 2-suppressive effects of helminths. However, progress regarding the mechanisms and molecules that are employed by helminths to modulate allergic inflammation has been relatively recent. The scavenging of alarmins and the modulation of lipid mediator pathways and macrophage function by helminth proteins have been identified as important immunoregulatory mechanisms targeting innate immunity in asthma and allergy. In addition, by regulating the activation of dendritic cells and by promoting regulatory T-cell responses, helminth proteins can counterregulate the adaptive T helper 2 cell response that drives allergic inflammation. Despite these insights, important open questions remain to be addressed before helminth molecules can be used for the prevention and treatment of asthma and other allergic diseases.

Keywords: allergy; asthma; helminth molecules; helminths; immune regulation; inflammation; macrophage; type 2 immunity.

FIGURE 1

Overview of immune regulatory helminth molecules and their mechanisms of action in mouse models of allergic airway inflammation and in human in vitro models. Immunomodulators from different helminths can act on a variety of cells ranging from innate to adaptive and effector immune cells. Blocking of signaling is shown by red arrows, induction by green, and modulation by spaced, gray arrows. AAI, allergic airway inflammation; AIP-2, anti-inflammatory protein 2; As, A. simplex; Av, A. vitae; Cys, cystatin; DC, dendritic cell; Ev, Extracellular vesicles; GDH, glutamate dehydrogenase; HDM, house dust mite; HpARI, H. polygyrus Alarmin Release Inhibitor; HpBARI, H. polygyrus Binds Alarmin Receptor and Inhibits; HpbE, H. polygyrus extract; Mφ, macrophage; MIF, macrophage migration inhibitory factor; Nb, N. brasiliensis; OVA, ovalbumin; PC, phosphocholine; SEA, schistosome soluble egg antigen; Sm, S. mansoni.