Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model

Smyth, Danielle J.; Ren, B; White, Madeleine P. J.; McManus, Caitlin M.; Webster, Holly; Shek, Vivien; Evans, Caroline; Pandhal, Jagroop; Fields, Francis J.; Maizels, Rick M.; Mayfield, Stephen P.

doi:10.1016/j.jbiotec.2021.08.006

Cited by 19 publications

(17 citation statements)

References 74 publications

(88 reference statements)

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“… 127 A Heligmosomoides polygyrus TGF-β mimic can directly bind to TGF-β receptors in humans and mice, and induce differentiation of Treg cells, which alleviates pathological damage in the allograft rejection and DSS-induced colitis models in mice. 128 , 129 Cell therapy using Treg cells to treat allergic asthma has been reported. Adoptive transfer of Treg cells from Trichinella spiralis -infected mice to OVA-treated mice showed significant anti-inflammatory effects.…”

Section: The Immunoregulatory Mechanisms Of Identified Helminth-derived Moleculesmentioning

confidence: 99%

Helminth Therapy for Immune-Mediated Inflammatory Diseases: Current and Future Perspectives

Shi¹,

Xu²,

Wang³

et al. 2022

JIR

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Inflammatory bowel disease and allergic asthma, as typical immune-mediated inflammatory diseases (IMIDs), are associated with immune imbalance caused by complex interactions among environmental, genetic and bacterial factors. The changing immune imbalance of IMIDs not only causes serious pathological damages but also increases the difficulty of treatment. Helminths or helminth-derived molecules have been increasingly employed to treat IMIDs due to their immunoregulatory ability. Since helminth infection is not an appropriate treatment direction due to the complex immunoregulation and safety concerns, one of the new therapies is to harness the immunoregulation induced by the identified helminth-derived molecules using immune indexes as a guide. This review discusses the pathogenesis of inflammatory bowel disease and allergic asthma, and summarizes the therapeutic effect of helminths and the immunoregulatory mechanisms induced by helminth-derived molecules proposing therapeutic regimens.

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Section: The Immunoregulatory Mechanisms Of Identified Helminth-derived Moleculesmentioning

confidence: 99%

Helminth Therapy for Immune-Mediated Inflammatory Diseases: Current and Future Perspectives

Shi¹,

Xu²,

Wang³

et al. 2022

JIR

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“…In recent studies, we have shown that TGM can mediate suppression of immune inflammation, for example in models of airway allergy (Chauché et al, 2022). We also established the ability of TGM to abate the severity of DSS colitis in mice, using high doses delivered orally through admixture with drinking water (Smyth et al, 2021). Focusing on colitis, we now evaluate in more depth the relative potencies of HES and TGM, using several different murine models of colitis (Kiesler et al, 2015), including inflammation induced with TNBS, and a T cell transfer model in which adaptive immune responses to intestinal antigens more closely represents human disease.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β,Hp-TGM

Smyth

White

Johnston

et al. 2023

Discovery Immunology

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In animal models of inflammatory colitis, pathology can be ameliorated by several intestinal helminth parasites, including the mouse nematode Heligmosomoides polygyrus. To identify parasite products that may exert anti-inflammatory effects in vivo, we tested H. polygyrus excretory-secretory (HES) products, as well as a recombinantly-expressed parasite protein, TGM, that functionally mimics the mammalian immunomodulatory cytokine TGF-β. HES and TGM showed a degree of protection in DSS-induced colitis, with a reduction in inflammatory cytokines, but did not fully block the development of pathology. HES also showed little benefit in a similar acute TNBS-induced model. However, in a T cell transfer-mediated model with RAG-deficient mice, HES reduced disease scores if administered throughout the first 2 or 4 weeks following transfer but was less effective if treatment was delayed until 14 days after T cell transfer. Recombinant TGM similarly dampened colitis in RAG-deficient recipients of effector T cells, and was effective even if introduced only once symptoms had begun to be manifest. These results are a promising indication that TGM may replicate, and even surpass, the modulatory properties of native parasite HES.

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“…Administration of recombinant S. japonicum cystatin also reduced inflammatory parameters and ameliorated the severity of the trinitrobenzene sulfonic acid (TNBS)-induced colitis ( 81 ). HpTGM from H. polygyrus is a TGF-β mimicry and suppresses intestinal inflammatory response ( 5 , 82 ). In Smyth’s study (2020), active HpTGM was recombinantly expressed by Chlamydomonas reinhardtii in order to be safely consumed orally in mice and humans.…”

Section: Potential Of Parasite-derived Immunomodulators As Drugs For ...mentioning

confidence: 99%

“…In Smyth’s study (2020), active HpTGM was recombinantly expressed by Chlamydomonas reinhardtii in order to be safely consumed orally in mice and humans. Oral administration of recombinant HpTGM regulated immune cells and ameliorated weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis ( 82 ).…”

Section: Potential Of Parasite-derived Immunomodulators As Drugs For ...mentioning

confidence: 99%

Parasitomimetics: Can We Utilize Parasite-Derived Immunomodulatory Molecules for Interventions to Immunological Disorders?

Nagai

Goto

2022

Front. Immunol.

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Because our immune system has ability to expel microorganisms invading our body, parasites need evolution to maintain their symbiosis with the hosts. One such strategy of the parasites is to manipulate host immunity by producing immunomodulatory molecules and the ability of parasites to regulate host immunity has long been a target of research. Parasites can not only manipulate host immune response specific to them, but also influence the host’s entire immune system. Such ability of the parasites may sometimes bring benefit to the hosts as many studies have indicated the “hygiene hypothesis” that a decreased opportunity of parasitic infections is associated with an increased incidence of allergy and autoimmune diseases. In other words, elucidating the mechanisms of parasites to regulate host immunity could be applied not only to resolution of parasitic infections but also to treatment of non-parasitic immunological disorders. In this review, we show how much progress has been made in the research on immunomodulation of host immunity by parasites. Here, we define the word ‘parasitomimetics’ as emulation of parasites’ immunomodulatory systems to solve immunological problems in humans and discuss potential applications of parasite-derived molecules to other diseases.

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Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model

Cited by 19 publications

References 74 publications

Helminth Therapy for Immune-Mediated Inflammatory Diseases: Current and Future Perspectives

Helminth Therapy for Immune-Mediated Inflammatory Diseases: Current and Future Perspectives

Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β,Hp-TGM

Parasitomimetics: Can We Utilize Parasite-Derived Immunomodulatory Molecules for Interventions to Immunological Disorders?

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