Identifying the immunomodulatory components of helminths

Shepherd, Catherine; Navarro, Séverine; Wangchuk, Phurpa; Wilson, David T.; Daly, Norelle L.; Loukas, Alex

doi:10.1111/pim.12192

Cited by 55 publications

(43 citation statements)

References 159 publications

(205 reference statements)

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“…Large proportions of proteases (38% of serine carboxypeptidases, 36% of trypsins, 23% of eukaryotic aspartyl proteases, and 18% of zinc carboxypeptidases) and protease inhibitors (33% of trypsin inhibitor-like cysteine-rich domain and 19% of Kunitz/Bovine pancreatic trypsin inhibitor domain) contained in the genome are found in the venom. 17% of Shk domain-containing proteins that are predicted to be toxins [4, 46] are present in the venom. A gene tree was constructed for Shk domain-containing proteins from S .…”

Section: Resultsmentioning

confidence: 99%

“…The immunomodulatory and pathogenic properties of parasitic nematodes are largely attributed to the excretory/secretory (ES) products they release during infection [3, 4]. ES products are complex mixtures and often include small molecules, proteins, and nucleic acids.…”

Section: Introductionmentioning

confidence: 99%

“…ES products are complex mixtures and often include small molecules, proteins, and nucleic acids. The complexity of these products and technical limitations in obtaining sufficient quantities for separation studies have resulted in current efforts often being focused on the most abundant components [Reviewed in 4]. Some functional studies evaluated individual ES components and have produced provocative results in animal models as vaccine candidates and as potential therapeutics in autoimmune diseases [5, 6].…”

Section: Introductionmentioning

confidence: 99%

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Activated entomopathogenic nematode infective juveniles release lethal venom proteins

et al. 2017

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Entomopathogenic nematodes (EPNs) are unique parasites due to their symbiosis with entomopathogenic bacteria and their ability to kill insect hosts quickly after infection. It is widely believed that EPNs rely on their bacterial partners for killing hosts. Here we disproved this theory by demonstrating that the in vitro activated infective juveniles (IJs) of Steinernema carpocapsae (a well-studied EPN species) release venom proteins that are lethal to several insects including Drosophila melanogaster. We confirmed that the in vitro activation is a good approximation of the in vivo process by comparing the transcriptomes of individual in vitro and in vivo activated IJs. We further analyzed the transcriptomes of non-activated and activated IJs and revealed a dramatic shift in gene expression during IJ activation. We also analyzed the venom proteome using mass spectrometry. Among the 472 venom proteins, proteases and protease inhibitors are especially abundant, and toxin-related proteins such as Shk domain-containing proteins and fatty acid- and retinol-binding proteins are also detected, which are potential candidates for suppressing the host immune system. Many of the venom proteins have conserved orthologs in vertebrate-parasitic nematodes and are differentially expressed during IJ activation, suggesting conserved functions in nematode parasitism. In summary, our findings strongly support a new model that S. carpocapsae and likely other Steinernema EPNs have a more active role in contributing to the pathogenicity of the nematode-bacterium complex than simply relying on their symbiotic bacteria. Furthermore, we propose that EPNs are a good model system for investigating vertebrate- and human-parasitic nematodes, especially regarding the function of excretory/secretory products.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activated entomopathogenic nematode infective juveniles release lethal venom proteins

et al. 2017

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“…For example, the human response to helminths is spectral, and only a subset might gain benefit from live infection; each helminth species inhabits a particular anatomic niche that might or might not affect the site of inflammatory disease; the dynamics of any protective effect in terms of parasite dose and duration of infection are unknown; and therapy of an established inflammatory disorder might require a particularly high parasite load or long-term infection. For each of these reasons, a more analytic approach of identifying immunomodulatory mechanisms and molecular mediators from helminths is advocated as the best strategy for developing new therapies inspired by the immunosuppressive capacities of parasites 100, 101, 102. By this means, individual molecular products can be assessed, validated, and developed as defined pharmaceuticals, which can then be delivered in a manner most consistent with the indication in question.…”

Section: Protection From Allergy Autoimmunity and Allograft Rejectionmentioning

confidence: 99%

Regulation of the host immune system by helminth parasites

Maizels

McSorley

2016

Journal of Allergy and Clinical Immunology

419

398

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Helminth parasite infections are associated with a battery of immunomodulatory mechanisms that affect all facets of the host immune response to ensure their persistence within the host. This broad-spectrum modulation of host immunity has intended and unintended consequences, both advantageous and disadvantageous. Thus the host can benefit from suppression of collateral damage during parasite infection and from reduced allergic, autoimmune, and inflammatory reactions. However, helminth infection can also be detrimental in reducing vaccine responses, increasing susceptibility to coinfection and potentially reducing tumor immunosurveillance. In this review we will summarize the panoply of immunomodulatory mechanisms used by helminths, their potential utility in human disease, and prospective areas of future research.

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“…One of these potential mechanisms is likely to rely on the production of immune-modulatory excretory/secretory products (ES) by hookworms, which include homologues of mammalian C-type lectins, galectins and cytokines91011; however, it is likely that other biological and environmental factors are involved in these processes. In particular, given the primary role played by gastrointestinal dysbiosis in the pathogenesis of CeD12, it has been proposed that one of the mechanisms by which hookworms can support intestinal immune homeostasis in inflammatory disorders (such as CeD), is via the alteration of the composition of the gut microbiota and relative abundance of individual microbial species81314151617.…”

mentioning

confidence: 99%

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease

Giacomin

Zakrzewski

Jenkins

et al. 2016

Sci Rep

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A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.

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Identifying the immunomodulatory components of helminths

Cited by 55 publications

References 159 publications

Activated entomopathogenic nematode infective juveniles release lethal venom proteins

Activated entomopathogenic nematode infective juveniles release lethal venom proteins

Regulation of the host immune system by helminth parasites

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease

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