Helminth Therapy for Autoimmune Diseases and Allergy

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Helminth Therapy for Autoimmune Diseases and Allergy Name Institution Date

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Background Helminth evolution equipped them with the capacity to subvert immune surveillance The are efficient modulators of the host’s immune system They suppress immune responses preventing inflammatory responses

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Autoimmunity and Allergy

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Autoimmunity is a condition in which the immune system mistakenly attacks the body cells. Allergies are the inappropriate response of the immune system to a harmless foreign substance

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Autoimmune diseases They are caused by immune responses against selfantigens Bacterial and viral infections are the major risk factors of autoimmune diseases Some common autoimmune conditions include: multiple sclerosis, diabetes, rheumatoid arthritis myocarditis

The burden of autoimmune diseases 09/12/2023

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Autoimmune diseases are a growing global problem They cause morbidity and mortality They affect over 8% of the population Their prevalence is higher in women than men Preventive measures of these disorders are not well understood.

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Standard treatment of autoimmune diseases

 Immunosuppressant and anti-inflammatory medications form the first line of treatment  These treatments can produce harmful side effects  Prolonged use can lead to cancer

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The process of Helminth Therapy

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Helminth therapy involves using intestinal worms to treat autoimmune conditions Helminths have an innate capability to tilt the hosts immune responses For instance they can tilt the immune response from Th1 to Th2/Treg,

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Cont… Helminths' potent host immunity modulation can be exploited to regulate inflammatory conditions related to dysregulated immune response Helminths exhibit an inverse relationship between the presence of the helminths and the inflammatory disease progression.

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Parasites-induced immune response

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 Helminths tamper with the host’s immune system  They target the T-Cell immune subsystem

 These parasites act on all phases of the host’s immune response including signaling, antigen recognition and processing, coagulation healing and remodeling, effector cell responses and adaptive processes.

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a). Neutralizing alarming signals Helminths have alarming release inhibitors which suppress the release of IL-33 The inhibitors bind to the inactive IL-33preventing its biding to receptors These responses prevent type-2 cell mediated inflammation

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b). Targeting macrophage and dendritic cell functions  Helminth molecules block the macrophage activation process  These molecules interfere with receptors, signaling, and antigen presentation  Signaling requires MyD88 adopter protein  Helminth excretory/secretory products induce MyD88 sequestration  Sequestration suppresses IL-33 and TLR signaling

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c. Polarization of the Th2 response parasites stimulate the release of various interleukin hormones ILs promote the polarization of the Th2 response Polarization prevents the body from eliciting a Th1or Th7 immune response Helminths also trigger immune-regulatory molecules like TGFβ and IL-10 production These molecules suppress inflammation

Helminth Secretory/Excretory products

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 Fig 1: Helminth secretory/excretory products effect on host immune cells (Smallwood et al. 2017)

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d). Immunomodulation  helminth infections depends on a type-2 cytokine response  Type-2 responses contribute to the “walling off” of larvae and eggs  Helminth infections induce immuno-regulatory mechanisms like increased regulatory T-cell production and Interleukin-10 production, leading to a highly antiinflammatory environment. .

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Application to Intestinal inflammation treatment

Helminth infections inhibit intestinal infections They modulate immune response to intestinal microflora

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Application to allergy treatment Researchers have reported beneficial health impacts of helminth infections on allergies Inoculation can decrease synthesis of

inflammatory cytokine

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Challenges of helminth therapy helminth therapy is controversial but slowly gaining acceptance Some helminth infections may cause major health problems Inoculation with helminths may worsen diseases

Clinicians use a small dose of parasitic worms to reduce associated risks

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Conclusion Helminth infection is a potent intervention for autoimmune disorders. Helminths activate immunoregulatory circuits

Helminth therapy is safer than standards treatments which produce adverse effects following prolonged use

References

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 Aribi, M. (Ed.). (2017). Immunopathogenesis and immune-based therapy for selected autoimmune disorders. BoD–Books on Demand.  Athari, S.S., (2018). Immunoregulatory aspects of immunotherapy. BoD – Books on Demand.  Chatzidionysiou, K. (Ed.). (2015). Autoimmunity: Pathogenesis, clinical aspects, and therapy of specific autoimmune diseases.

BoD–Books on Demand.  Helmby, H. (2015). Human helminth therapy to treat inflammatory disorders-where do we stand?. BMC Immunology, 16(1), 1-5. https://doi.org/10.1186/s12865-015-0074-3  Hoffmann, J. H., & Enk, A. H. (2017). High ‐dose intravenous immunoglobulins for the treatment of dermatological autoimmune diseases. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 15(12), 1211-1226. http://DOI:10.1111/ddg.13389  Maizels, R. M. (2016). Parasitic helminth infections and the control of human allergic and autoimmune disorders. Clinical Microbiology and Infection, 22(6), 481-486. https://doi.org/10.1016/j.cmi.2016.04.024  Maizels, R. M., Smits, H. H., & McSorley, H. J. (2018). Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules. Immunity, 49(5), 801–818. https://doi.org/10.1016/j.immuni.2018.10.016  Maruszewska-Cheruiyot, M., Donskow-Łysoniewska, K., & Doligalska, M. (2018). Helminth therapy: Advances in the use of parasitic worms against inflammatory bowel diseases and its challenges. Helminthologia, 55(1), 1–11. https://doi.org/10.1515/helm-2017-0048  Smallwood, T. B., Giacomin, P. R., Loukas, A., Mulvenna, J. P., Clark, R. J., & Miles, J. J. (2017). Helminth immunomodulation in autoimmune disease. Frontiers in immunology, 8, 453. https://doi.org/10.3389/fimmu.2017.00453  Sun, S., Li, H., Yuan, Y., Wang, L., He, W., Xie, H., ... & Yang, X. (2019). Preventive and therapeutic effects of Trichinella spiralis adult extracts on allergic inflammation in an experimental asthma mouse model. Parasites & Vectors, 12(1), 1-10. https://doi.org/10.1186/s13071-019-3561-1  Terziroli, B, B, Mieli-Vergani, G, & Vergani D. (2017). Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments. World J Gastroenterol. 23(33), 6030-6048. http://doi:10.3748/wjg.v23.i33.6030  Wammes, L. J., Hamid, F., Wiria, A. E., May, L., Kaisar, M. M., Prasetyani-Gieseler, M. A., ... & Yazdanbakhsh, M. (2016).

Community deworming alleviates geohelminth-induced immune hyporesponsiveness. Proceedings of the National Academy of Sciences, 113(44), 12526-12531. https://doi.org/10.1073/pnas.1604570113  Yoosuf, S., & Makharia, G. K. (2019). Evolving therapy for celiac disease. Frontiers in Pediatrics, 7, 193. https://doi.org/10.3389/fped.2019.00193