Parasite-Derived Proteins for the Treatment of Allergies and Autoimmune Diseases

Abstract

The morbidity associated with atopic diseases and immune dysregulation disorders such as asthma, food allergies, multiple sclerosis, atopic dermatitis, type 1 diabetes mellitus, and inflammatory bowel disease has been increasing all around the world over the past few decades. Although the roles of non-biological environmental factors and genetic factors in the etiopathology have been particularly emphasized, they do not fully explain the increase; for example, genetic factors in a population change very gradually. Epidemiological investigation has revealed that the increase also parallels a decrease in infectious diseases, especially parasitic infections. Thus, the reduced prevalence of parasitic infections may be another important reason for immune dysregulation. Parasites have co-evolved with the human immune system for a long time. Some parasite-derived immune-evasion molecules have been verified to reduce the incidence and harmfulness of atopic diseases in humans by modulating the immune response. More importantly, some parasite-derived products have been shown to inhibit the progression of inflammatory diseases and consequently alleviate their symptoms. Thus, parasites, and especially their products, may have potential applications in the treatment of autoimmune diseases. In this review, the potential of parasite-derived products and their analogs for use in the treatment of atopic diseases and immune dysregulation is summarized.

Helminth parasites and immune regulation

“…Some of the soluble proteins, lipids, and carbohydrates present in the ES products have been shown to have immunomodulatory activity 64 , 65 . The list of helminth-derived immunomodulatory molecules that evoke a regulatory phenotype among innate and adaptive immune cells has been increasing over the last decade 9 , 10 , 41 , 64 – 66 .…”

Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development

“…Helminth parasites are well known for their capacity to modulate the parasite-directed host immune response (1,2); with long-standing infection these parasites modulate the host response to bystander antigens/pathogens (3)(4)(5), to allergic diseases (6,7), and to both orally and parenterally administered vaccines (8,9). More controversially and largely on the basis of murine models, helminths have been implicated in ameliorating the severity of inflammatory bowel disease (10,11), diabetes (12,13), and arthritis (14), findings that have driven the concept of using these parasites or their excreted/secreted products, including their extracellular vesicles (15), for the treatment of inflammatory diseases (16,17). However, the mechanisms by which helminths mediate these protective functions remained poorly defined.…”

Immunomodulating effect of Schistosoma mansoni soluble egg antigen on course of induced diabetes mellitus in experimental mice

“…During its pathogenesis, lymphocyte infiltration into the islets is not only an initial characteristic of pathology, but also a fundamental step in disease development [3] . The "hygiene hypothesis" postulates that the increased incidence of autoimmune diseases such as diabetes in the developed world is the result of decreased exposure to infectious agents [1,25,26] . Among the first researches to validate the protecting consequence of helminth infections on diabetes was done employing S. mansoni infection in NOD mice by Cooke et al, [29] , who prompted us to use in our study SEA as a protective agent.…”

“…Mice engineered to over-express IL-10 (by gene transfer) recover insulin sensitivity and are moderately protected from high fat diet-induced obesity and glucose intolerance and reduce lymphoid infiltration in pancreatic islets that prevent their destruction [21][22][23][24] . The hygiene hypothesis was first described by Strachan [5] ; it assumes that the higher incidence of autoimmune diseases in the industrialized countries is the consequence of low contact to infectious agents [25,26] .…”