Trends in Parasitology
OpinionThe Untapped Pharmacopeic Potential of Helminths
Section snippets
Helminth Infections – ‘World Wide Worms’
It has been estimated that at least 1.8 billion people are infected with helminths (see Glossary) [1]. Since helminth infections disproportionately affect low-income populations in developing regions of Africa, Asia, and America, they belong to a group of diseases referred to as the ‘major neglected tropical diseases’. According to the Global Burden of Disease Study 2016, helminth infections cause more than 10 million disability-adjusted life years (DALYs) [2]. Although highly parasitized
Immune-Related Disorders
Epidemiological studies have shown a rise in prevalence of immune-related disorders, including autoimmune and allergic diseases. Inflammatory bowel disease (IBD) [encompassing Crohńs disease (CD) and ulcerative colitis (UC)], type 1 diabetes (T1D), multiple sclerosis (MS), and rheumatoid arthritis (RA) are just a few examples of more than 80 autoimmune diseases that affect approximately 5–8% of the population worldwide, with the highest prevalence in the developed world [3]. Since these chronic
Worm Influences on Immunological Disorders
During millions of years of parasite–host coevolution, helminths have developed multiple mechanisms to modulate the host́s inflammatory responses and ensure their long-term survival in various hosts [5]. Not surprisingly, hundreds of immune-response genes were selectively favoured under the pressure of helminth infections [6]. Recently, a comprehensive meta-analysis of publicly available gene-expression datasets revealed a gene-expression signature across multiple helminth species and host
Helminth Therapy – ‘Domestication’ of the Worm
Worms as therapeutic agents have been applied in numerous animal models of diseases that have inflammatory or autoimmune etiology. Despite highly encouraging data from experimental animal models for IBD, MS, T1D, RA, and systemic lupus erythematosus that suggest preventive and therapeutic benefits [20], clinical trials in humans have lead to rather sobering results so far. For asthma and allergic rhinitis no benefit from helminth administration (Trichuris suis ova or hookworm infection) was
Hashtag # Helminth Therapy
Helminth replacement therapy as a form of probiotic therapy has gained much attention in mainstream media. Patients looking for alternative therapy for their maladies learn about helminth therapy through web-based community networks or social media [35]. There are multitudes of web sites promoting the therapeutic use of living parasites (‘worm smoothies’). Unfortunately, sometimes only self-treatment stories, case studies, or small clinical trials are presented that show beneficial responses to
E/S Products to Combat Immunological Disorders
Considering the biological complexity of metazoan parasites, using whole organisms or even purified protein fractions as therapeutic drugs is undesirable due to scalability and low stability as well as safety issues. Consequently, a less controversial and more palatable alternative to helminth therapy is the potential therapeutic use of helminth-derived immune-modulatory molecules.
Within their host, helminths release a rich mixture of proteins, glycoproteins, and low-molecular-weight compounds
Novel Therapeutic Approaches in Transfer and Delivery – ‘Signed Sealed Delivered’
The discovery of exosome-like extracellular vesicles that deliver bioactive macromolecules for intercellular communication has attracted considerable interest, particularly due to their role as mediators within the immune system [71]. EVs secreted by various helminths are effective vehicles for delivering proteins, lipids, and nucleic acids and other small molecules in a protected manner, thereby mediating cross-species communication as part of the host–parasite interaction [72]. The cargo of
Concluding Remarks and Future Perspectives
The remarkable advances in mass spectrometry-based proteomics have enabled the elucidation of whole secretomes (secretomics) from numerous helminths and have lead to the identification of the molecular components of the host–helminth interface. Furthermore, multitechnological integrative approaches that involve genomic, transcriptomic, and proteomic methods, combined with bioinformatics strategies, are producing a wealth of information at a very large scale, a valuable goldmine that serves as
Acknowledgments
We apologize to authors of primary literature for failing to cite their work directly owing to limitations in the number of references.
Glossary
- Excretory–secretory (ES) products
- helminths release a diverse mixture of proteins, glycans, and low-molecular-weight molecules considered to be readily exposed to the host́s immune system, many of which have immunomodulatory properties.
- Group 2 innate lymphoid cells (ILC2)
- respond to IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), and produce early cytokines IL-13, IL-4, and IL-5.
- Gut-on-a-chip
- a 3D cell-culture model that mimicks key properties of the human gut, such as multicellular
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Cited by (34)
Immunomodulatory effects of parasites on autoimmunity
2022, Translational Autoimmunity: Treatment of Autoimmune DiseasesUsing Caenorhabditis elegans to produce functional secretory proteins of parasitic nematodes
2022, Acta TropicaCitation Excerpt :However, main drawbacks are high production costs and demanding cultural conditions (Khan, 2013). While many of these heterologous systems have been successfully used to obtain soluble and bioactive helminth proteins for functional or immunological studies (Geldhof et al., 2007b; Kahl et al., 2018), the free living nematode Caenorhabditis elegans also has the potential to be an excellent host for the heterologous expression of ESPs. For nematode parasitologists C. elegans is a “user-friendly” model system to learn about the essentials of nematode biology.
Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model
2021, Journal of BiotechnologyCitation Excerpt :There was an increase in all DSS-treated mice seen in the MLN (Supplementary Fig. 5B) but not the Peyer’s patches (Supplementary Fig. 5C). Immuno-modulatory parasites are increasingly recognized as treasure chests of novel, biologically active products with therapeutic potential, particularly for inflammatory disorders which are increasingly prevalent in industrialized societies (Johnston et al., 2009; Kahl et al., 2018; Maizels et al., 2018). Among the most severe of these “diseases of modernity” are inflammatory bowel diseases, for which no curative therapy is yet available (Kaser et al., 2010).
Onchocerciasis (river blindness) – more than a century of research and control
2021, Acta TropicaCitation Excerpt :In addition, the parasite synthesizes and releases a myriad of intercepting excretory/secretory (E/S) molecules, via extracellular vesicles or directly. These molecules include antioxidants, protease-inhibitors, carbohydrate- and lipid-binding molecules and cytokine regulators, which mitigate and detoxify the offending host's components and recently, in addition, have been suggested as possible immunomodulators suppressing inflammatory diseases (Hewitson et al., 2009; Ditgen et al., 2014; Kahl et al., 2018; Njume et al., 2019). O. volvulus microfilariae also release matrix-degrading serine and metalloproteases which can degrade components of the dermal extracellular matrix and elastic fibres of host tissue, as observed in chronic onchocerciasis (Haffner et al., 1998).
Gut microecology: Why our microbes could be key to our health
2020, Biomedicine and PharmacotherapyFasciola hepatica-derived molecules as potential immunomodulators
2020, Acta Tropica