Therapeutic potential of larval excretory/secretory proteins of the pig whipworm<i>Trichuris suis</i>in allergic disease

Ebner, Friederike; Hepworth, Matthew R.; Rausch, Sebastian; Janek, Katharina; Niewienda, Agathe; Kühl, Anja A.; Henklein, Petra; Lucius, Richard; Hamelmann, Eckard; Hartmann, Susanne

doi:10.1111/all.12496

Cited by 48 publications

(49 citation statements)

References 38 publications

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“…In accordance with our results, previous studies showed the therapeutic potentials of helminths in resistance from allergic asthma via the expansion of CD4 + CD25 + FOXP3 + regulatory cells and IL-10 and TGF-β production [21, 59]. For example, the larval ES products of T. suis have immunomodulatory functions and could prevent OVA-induced allergic asthma in a IL-10 dependent manner [20]. Filarial cystatin, a secreted protease inhibitor of filarial nematodes ( Acanthocheilonema viteae ) reduced IL-4 production and suppressed OVA-induced allergic airway inflammation through a mechanism involving anti-inflammatory cytokine IL-10.…”

Section: Discussionsupporting

confidence: 91%

“…Immunoregulatory cytokines have been implicated in parasite-derived modulation of host immunity during chronic infection [15, 36]. It was suggested that parasite-derived regulatory cytokines may be involved in blocking inflammatory responses such as allergic asthma [17, 20]. This hypothesis was supported by demonstrating that administration of somatic products generated significantly higher levels of IL-10 and TGF-β (Fig.…”

Section: Discussionmentioning

confidence: 95%

“…Both epidemiological [19] and experimental [20, 21] studies have revealed that exposure to helminth infection evoke suppressive effects on the development of a broad spectrum of immune-mediated diseases such as allergy and autoimmune diseases. These results provide a supportive evidence for confirmation of hygiene hypothesis [22], the proposition that helminth infection can impair immunological reactivity.…”

Section: Introductionmentioning

confidence: 99%

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Somatic extracts of Marshallagia marshalli downregulate the Th2 associated immune responses in ovalbumin-induced airway inflammation in BALB/c mice

et al. 2017

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BackgroundRecently the role of gastrointestinal nematodes in modulating the immune responses in inflammatory and immune-mediated conditions such as allergy and autoimmune diseases has been introduced. This is mainly due to the suppressive effects of somatic and excretory secretory (ES) products of nematodes on the immune responses. In this study, we evaluated the immunomodulatory potentials of somatic products of Marshallagia marshalli, a gastrointestinal nematodes of sheep, to suppress the immune-mediated responses in a murine model of allergic airway inflammation. BALB/c mice were intraperitoneally (IP) sensitized with ovalbumin (OVA)/Alum and then challenged with 1% OVA. Somatic products of M. marshalli were administered during each sensitization. The effects of somatic products on development of allergic airway inflammation were evaluated by analyzing inflammatory cells recruitment, histopathological changes, cytokines production (IL-4, IL-13, IL-10, TGF-β) and serum antibody titers (IgG1, IgG2a).ResultsSomatic products of M. marshalli were able to suppress the induction of allergic airway inflammation in mice. Modulation of Th2 type responses (IL-4, IL-13, IgG1) via upregulations of IL-10 and TGF-β production was observed after injection of somatic products of M. marshalli. In addition, inflammatory cells infiltration and pathological disorders were significantly diminished following administration of somatic products.ConclusionsOur data raised the possibility that helminths could be a potential therapeutic candidate to alleviate the inflammatory conditions in allergic asthma. According to these results, we concluded that M. marshalli may contain immune-modulatory molecules that attenuate allergic airway inflammation via induction of regulatory cytokines. Further investigations are required to identify molecules that might have potentials for development of novel therapeutic targets.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Somatic extracts of Marshallagia marshalli downregulate the Th2 associated immune responses in ovalbumin-induced airway inflammation in BALB/c mice

et al. 2017

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“…The ‘old friends’ hypothesis seeks to understand the evolutionary factors which have shaped the immune system and to explain correlations between lifestyles in the developed world and modern ‘epidemics’ which are due to immunological misbalance (4-6). Promising data have suggested that ‘worm therapy’ may bring advantages to some patients with Crohn’s disease or allergies (7,8); however, such approaches are controversial. Nevertheless, crude extracts even of Caenorhabditis elegans were shown to induce a glycan-dependent Th2 response (9), whereas the excretory-secretory products of some nematodes also have immunomodulatory activity (10).…”

Section: Introductionmentioning

confidence: 99%

Bisecting Galactose as a Feature of N-Glycans of Wild-type and Mutant Caenorhabditis elegans

Yan

Brecker

Jin

et al. 2015

Molecular & Cellular Proteomics

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The N-glycosylation of the model nematode Caenorhabiditis elegans has proven to be highly variable and rather complex; it is an example to contradict the existing impression that ‘simple’ organisms possess also a rather simple glycomic capacity. In previous studies in a number of laboratories, N-glycans with up to four fucose residues have been detected. However, although the linkage of three fucose residues to the N,N′-diacetylchitobiosyl core has been proven by structural and enzymatic analyses, the nature of the fourth fucose has remained uncertain. By constructing a triple mutant with deletions in the three genes responsible for core fucosylation (fut-1, fut-6 and fut-8), we have produced a nematode strain lacking products of these enzymes, but still retaining maximally one fucose residue on its N-glycans. Using mass spectrometry and HPLC in conjunction with chemical and enzymatic treatments as well as NMR, we examined a set of α-mannosidase-resistant N-glycans. Within this glycomic sub-pool, we can reveal that the core β-mannose can be trisubstituted and so carries not only the ubiquitous α1,3- and α1,6-mannose residues, but also a ‘bisecting’ β-galactose which is substoichiometrically modified with fucose or methylfucose. In addition, the α1,3-mannose can also be α-galactosylated. Not only do these residues constitute novel modifications of N-glycans, but these features may well be targets of nematoxic proteins produced as defence molecules by various fungal species.

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“…First, in most investigations aimed to study helminth-derived antigens, it is an important issue that ES products used in such an experimental model, should be lipopolysaccharide (LPS) free (2,3). Thus prior to study on immunoregulatory effects of helminth-derived antigens, LPS content in ES should be determined by endotoxin detection assays such as Limulus Amebocyte Lysate test.…”

Section: Dear Editormentioning

confidence: 99%

What should be taken into account during study on immunoregulatory effects of helminths: a critical analyzing on “Downregulation of immune responses in asthmatic patients by ES products of Marshallagia marshalli”

Zakeri

Haghparast

2015

Clinical Respiratory J

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Therapeutic potential of larval excretory/secretory proteins of the pig whipwormTrichuris suisin allergic disease

Cited by 48 publications

References 38 publications

Somatic extracts of Marshallagia marshalli downregulate the Th2 associated immune responses in ovalbumin-induced airway inflammation in BALB/c mice

Somatic extracts of Marshallagia marshalli downregulate the Th2 associated immune responses in ovalbumin-induced airway inflammation in BALB/c mice

Bisecting Galactose as a Feature of N-Glycans of Wild-type and Mutant Caenorhabditis elegans

What should be taken into account during study on immunoregulatory effects of helminths: a critical analyzing on “Downregulation of immune responses in asthmatic patients by ES products of Marshallagia marshalli”

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