Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse
- Publication Type:
- Journal Article
- Citation:
- PLoS ONE, 2014, 9 (1)
- Issue Date:
- 2014-01-21
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author |
Lund, ME |
en_US |
dc.contributor.author |
O'Brien, BA |
en_US |
dc.contributor.author | Hutchinson, AT | en_US |
dc.contributor.author |
Robinson, MW |
en_US |
dc.contributor.author |
Simpson, AM |
en_US |
dc.contributor.author | Dalton, JP | en_US |
dc.contributor.author |
Donnelly, S |
en_US |
dc.date.available | 2013-12-13 | en_US |
dc.date.issued | 2014-01-21 | en_US |
dc.identifier.citation | PLoS ONE, 2014, 9 (1) | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/36730 | |
dc.description.abstract | Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFb and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro , FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment. © 2014 Lund et al. | en_US |
dc.relation | http://purl.org/au-research/grants/nhmrc/1010197 | |
dc.relation.ispartof | PLoS ONE | en_US |
dc.relation.isbasedon | 10.1371/journal.pone.0086289 | en_US |
dc.subject.classification | General Science & Technology | en_US |
dc.subject.mesh | Pancreas | en_US |
dc.subject.mesh | Lymph Nodes | en_US |
dc.subject.mesh | Macrophages, Peritoneal | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Mice, Inbred NOD | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Helminths | en_US |
dc.subject.mesh | Fasciola hepatica | en_US |
dc.subject.mesh | Diabetes Mellitus, Experimental | en_US |
dc.subject.mesh | Diabetes Mellitus, Type 1 | en_US |
dc.subject.mesh | Transforming Growth Factor beta | en_US |
dc.subject.mesh | Lectins | en_US |
dc.subject.mesh | Autoantibodies | en_US |
dc.subject.mesh | Cell Differentiation | en_US |
dc.subject.mesh | Autoimmunity | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | T-Lymphocytes, Regulatory | en_US |
dc.subject.mesh | beta-N-Acetylhexosaminidases | en_US |
dc.subject.mesh | Interferon-gamma | en_US |
dc.subject.mesh | Antigens, CD274 | en_US |
dc.subject.mesh | B7-H1 Antigen | en_US |
dc.title | Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 1 | en_US |
utslib.citation.volume | 9 | en_US |
utslib.for | 060406 Genetic Immunology | en_US |
utslib.for | 0601 Biochemistry and Cell Biology | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
utslib.copyright.status | open_access | |
pubs.issue | 1 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 9 | en_US |
Abstract:
Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFb and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro , FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment. © 2014 Lund et al.
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