Colonization with <i>Heligmosomoides polygyrus</i> Suppresses Mucosal IL-17 Production

Elliott, David E.; Metwali, Ahmed; Leung, John; Setiawan, Tommy; Blum, Arthur M.; Ince, M. Nedim; Bazzone, Lindsey E.; Stadecker, Miguel J.; Urban, Joseph F.; Weinstock, Joel V.

doi:10.4049/jimmunol.181.4.2414

Cited by 104 publications

(92 citation statements)

References 35 publications

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“…1 Collectively, these studies have shown that as a consequence of the host response to infection with helminth parasites, there is mobilization of transforming growth factor (TGF)-␤, interleukin (IL)-10, Foxp3 ϩ regulatory T cells, alternatively activated macrophages, and inhibition of IL-17-and interferon (IFN)-␥-driven events: one, or a combination, of these events could block the development of autoimmune and inflammatory disorders. [2][3][4][5][6][7] These findings have been complemented by intriguing data suggesting that infection with viable parasitic nematodes could be a treatment for patients with inflammatory bowel disease (IBD) 8 or asthma, 9 whose condition is not managed by conventional therapies.…”

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confidence: 87%

Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta

Wang

Fernando²,

Leung³

et al. 2010

The American Journal of Pathology

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confidence: 87%

Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta

Wang

Fernando²,

Leung³

et al. 2010

The American Journal of Pathology

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“…Furthermore, it has been reported that colonization with Heligmosomoides polygyrus suppresses IL-17 production in the mesenteric lymph node (14). Experimental studies in mouse models have also demonstrated that helminth infections can ameliorate autoimmune diseases (15)(16)(17), and although Th2 and antiinflammatory cytokines have been implicated in protection, the role of Treg cells is still unclear.…”

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confidence: 99%

Infection with a Helminth Parasite Attenuates Autoimmunity through TGF-β-Mediated Suppression of Th17 and Th1 Responses

Walsh

Brady

Finlay

et al. 2009

The Journal of Immunology

257

201

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The lower incidence of allergy and autoimmune diseases in developing countries has been associated with a high prevalence of parasitic infections. Here we provide direct experimental evidence that parasites can exert bystander immunosuppression of pathogenic T cells that mediate autoimmune diseases. Infection of mice with Fasciola hepatica resulted in recruitment of dendritic cells, macrophages, eosinophils, neutrophils, and CD4+ T cells into the peritoneal cavity. The dendritic cells and macrophages in infected mice expressed IL-10 and latency-associated peptide, and they had low surface expression of costimulatory molecules and/or MHC class II. Furthermore, most CD4+ T cells in the peritoneal cavity of infected mice secreted IL-10, but not IFN-γ or IL-4. There was a less significant expansion of CD4+Foxp3+ T cells. F. hepatica-specific Tr1-type clones generated from infected mice suppressed proliferation and IFN-γ production by Th1 cells. Infection was associated with suppression of parasite-specific Th1 and Th2 responses, which was reversed in IL-10-defective mice. Infection with F. hepatica also exerted bystander suppression of immune responses to autoantigens and attenuated the clinical signs of experimental autoimmune encephalomyelitis. Protection was associated with suppression of autoantigen-specific IFN-γ and IL-17 production. The suppression of Th1 and Th17 responses and attenuation of experimental autoimmune encephalomyelitis by F. hepatica was maintained in IL-10−/− mice but was reversed by neutralization of TGF-β in vivo. Our study provides evidence that F. hepatica-induced IL-10 subverts parasite-specific Th1 and Th2 responses, but that F. hepatica-induced TGF-β plays a critical role in bystander suppression of autoantigen-specific Th1 and Th17 responses that mediate autoimmune diseases.

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“…Remarkably, MS-associated disease activity increases after treatment with anti-helminthic drugs (3). Studies in mouse models have demonstrated that infection with helminth parasites protects against autoimmune diseases mediated by IL-17-or IFN-g-secreting T cells (4)(5)(6)(7). We have reported that live infection with the helminth parasite Fasciola hepatica attenuated the clinical severity of experimental autoimmune encephalomyelitis (EAE) in a TGF-b-dependent manner and was associated with the expansion of Tregs (7).…”

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confidence: 99%

Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia

Finlay

Stefańska

Walsh

et al. 2016

The Journal of Immunology

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Epidemiologic studies in humans have demonstrated that infection with helminth parasites is associated with a reduced risk of developing autoimmune diseases. Mechanistic studies in mice have linked the protective effect of helminths on autoimmunity to the suppressive activity of helminth-induced regulatory T cells (Tregs) or Th2 cells. In this study, we demonstrate that treatment of mice with Fasciola hepatica excretory-secretory products (FHES) attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Protection was associated with a significant reduction in the infiltration of pathogenic Th1 and Th17 cells into the brain. Although FHES enhanced anti-inflammatory cytokine and Th2 responses, protection against EAE was independent of IL-4, IL-10, and Tregs. However, administration of FHES induced production of the type 2 cytokines IL-33 and IL-5, which promoted accumulation of eosinophils. FHES-induced expansion of eosinophils and protection against EAE was lost in IL-33−/− mice and upon neutralization of IL-5. Furthermore, transfer of FHES-induced or IL-33–induced eosinophils conferred protection against EAE. In addition, treatment of mice with recombinant IL-33 attenuated autoimmunity, and this was dependent on IL-5. To our knowledge, this study is the first to report a role for helminth-induced IL-5 and IL-33 in protection against autoimmunity.

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Colonization with Heligmosomoides polygyrus Suppresses Mucosal IL-17 Production

Cited by 104 publications

References 35 publications

Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta

Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta

Infection with a Helminth Parasite Attenuates Autoimmunity through TGF-β-Mediated Suppression of Th17 and Th1 Responses

Helminth Products Protect against Autoimmunity via Innate Type 2 Cytokines IL-5 and IL-33, Which Promote Eosinophilia

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