• Biological sciences
• Health sciences
• Virology

• Clinical trials
• Dose escalation
• Helminth
• Inflammation
• Self-treatment

Allergic diseases are increasing at an alarming rate worldwide, particularly in developed countries. In contrast, there is a decrease in the prevalence of helminthic infections and other neglected diseases. The hygiene hypothesis elaborates parasitic infection, and allergy-associated diseases have an inverse relationship. Acute helminthic infection and allergic reaction stimulate Type 2 helper cells (Th2) immune response with up-regulation of cytokines IL-4-, IL-5-, and IL-13-mediated IgE and mast cell production, as well as eosinophilia. However, people who chronically suffer from helminthic infections are demarcated through polarized Th2 resulting in alternative macrophage activation and T regulatory response. This regulatory system reduces allergy incidence in individuals that are chronically diseased through helminth. As a result, the excretory-secretory (ES) substance derived from parasites and extracellular vesicular components can be used as a novel therapeutic modality of allergy. Therefore, the aim of this review meticulously explored the link between helminth infection and allergy, and utilization of the helminth secretome for therapeutic immunomodulation.

• IgE
• Treg
• allergy
• helminth
• hygiene hypothesis
• immunotherapy

• disease ecology
• host-parasite interaction
• immune system
• pathogen
• resistance
• stress
• susceptibility

• drug delivery
• immunomodulation
• nanomedicine
• parasites
• vaccines

Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity, altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings, such as inflammatory bowel disease (IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies, we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use, but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs, since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease, such as the importance of the specific species of helminths used, appropriate dosing regimens, optimal timing of treatment, the role of host genetics, diet, environment, and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method, especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.

• Helminths
• Strongyloidiasis
• Immunology
• Inflammation
• Inflammatory bowel diseases
• Intestinal diseases
• Intestinal permeability
• Celiac disease

• Animals
• Biological Products/therapeutic use
• Biological Therapy/adverse effects
• Biological Therapy/methods
• Celiac Disease/immunology
• Celiac Disease/therapy
• Clinical Trials as Topic
• Complementary Therapies/adverse effects
• Complementary Therapies/methods
• Humans
• Hygiene Hypothesis
• Immunotherapy/adverse effects
• Immunotherapy/methods
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/therapy
• Intestinal Mucosa/metabolism
• Permeability
• Strongyloides stercoralis/immunology
• Strongyloides stercoralis/metabolism
• Treatment Outcome

Current iterations of the hygiene hypothesis suggest an adaptive role for helminth parasites in shaping the proper maturation of the immune system. However, aspects of this hypothesis are based on assumptions that may not fully account for realities about human helminth infections. Such realities include evidence of causal associations between helminth infections and asthma or inflammatory bowel disease as well as the fact that helminth infections remain widespread in the United States, especially among populations at greatest risk for inflammatory and autoimmune diseases.

• Animals
• Asthma/parasitology
• Autoimmune Diseases/parasitology
• Autoimmune Diseases/therapy
• Helminthiasis/immunology
• Helminths/immunology
• Humans
• Hygiene Hypothesis
• Iatrogenic Disease
• Inflammatory Bowel Diseases/parasitology
• Randomized Controlled Trials as Topic

• T32 AI055413 NIAID NIH HHS

Parasite-derived molecules with immunomodulatory properties, which have been optimised during host-parasite co-evolution, exhibit potential applications as novel immunotherapeutics. We have previously demonstrated that Schistosoma japonicum HSP60-derived peptide SJMHE1 induces CD4⁺CD25⁺ regulatory T-cells (Tregs) and that adoptively transferred SJMHE1-induced CD4⁺CD25⁺ Tregs inhibit delayed-type hypersensitivity (DTH) in mice. However, multiple concerns regarding this method render this treatment unsuitable. To gain further insights into the potential effects of SJMHE1, we used ovalbumin (OVA)-induced DTH and evaluated the effect of SJMHE1 on DTH mice.

BALB/c mice were sensitised with OVA alone or combined with SJMHE1 and then challenged with OVA to induce DTH. We first analysed the potential effects of SJMHE1 by measuring DTH responses, T-cell responses, cytokine secretion, and Treg proportions. We then evaluated the expression levels of IL-10 and TGF-β1 in CD4⁺CD25⁺ T-cells during DTH and Treg generation to identify the mechanism by which SJMHE1 suppresses DTH.

SJMHE1 modulated the effector response against OVA-induced DTH and stimulated the production of the anti-inflammatory cytokines IL-10 and TGF-β1 in immunised mice through a mechanism involving CD4⁺CD25⁺ Tregs. SJMHE1-induced CD4⁺CD25⁺ Tregs expressed high levels of CTLA-4, IL-10, and TGF-β1, which substantially contributed to the suppressive activity during DTH. The administration of SJMHE1 to DTH in mice led to the expansion of CD4⁺CD25⁺ Tregs from CD4⁺CD25⁻ T-cells in the periphery, which inhibited DTH responses.

Our study proves that the parasite-driven peptide suppresses DTH in mice, which may confer a new option for inflammation treatment.

• Delayed-type hypersensitivity
• SJMHE1
• Schistosoma japonicum-derived peptide
• Suppress

Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans.

• Body weight
• Faecal egg count
• Gastrointestinal nemathelminths
• Goat
• Sheep

• Adolescent
• Adult
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Infant, Newborn
• Leishmaniasis, Visceral/diagnosis
• Leishmaniasis, Visceral/epidemiology
• Leishmaniasis, Visceral/mortality
• Male
• Middle Aged
• Prognosis
• Risk Factors
• Young Adult

In order to establish long-lasting infections in their mammalian host, filarial nematodes have developed sophisticated strategies to dampen their host’s immune response. Proteins that are actively secreted by the parasites have been shown to induce the expansion of regulatory T cells and to directly interfere with effector T cell function. Here, we analyze the suppressive capacity of Onchocercavolvulus-derived excreted/secreted proteins. Addition of two recombinant O. volvulus proteins, abundant larval transcript-2 (OvALT-2) and novel larval transcript-1 (OvNLT-1) to cell cultures of T cell receptor transgenic CD4⁺ and CD8⁺ T cells suppressed antigen-specific stimulation in vitro. Ovalbumin-specific CD4⁺ DO11.10 and OT-II T cells that had been stimulated with their cognate antigen in the presence of OvALT-2 or OvNLT-1 displayed reduced DNA synthesis quantified by ³H-thymidine incorporation and reduced cell division quantified by CFSE dilution. Furthermore, the IL-2 and IFN-γ response of ovalbumin-specific CD8⁺ OT-I T cells was suppressed by OvALT-2 and OvNLT-1. In contrast, another recombinant O. volvulus protein, microfilariae surface-associated antigen (Ov103), did not modulate T cell activation, thus serving as internal control for non-ESP-mediated artifacts. Suppressive capacity of the identified ESP was associated with induction of apoptosis in T cells demonstrated by increased exposure of phosphatidylserine on the plasma membrane. Of note, the digestion of recombinant proteins with proteinase K did not abolish the suppression of antigen-specific proliferation although the suppressive capacity of the identified excreted/secreted products was not mediated by low molecular weight contaminants in the undigested preparations. In summary, we identified two suppressive excreted/secreted products from O. volvulus, which interfere with the function of antigen-specific T cells in vitro.

• Animals
• Fish Diseases/immunology
• Fishes/immunology
• Host-Parasite Interactions/immunology
• Intestines/immunology
• Intestines/parasitology
• Larva
• Mammals/immunology
• Nematoda/immunology
• Nematode Infections/immunology
• Nematode Infections/veterinary