Infection with a Helminth Parasite Prevents Experimental Colitis via a Macrophage-Mediated Mechanism

Smith, Philip; Mangan, Niamh E.; Walsh, Caroline; Fallon, Rosie E.; McKenzie, Andrew N. J.; Rooijen, Nico van; Fallon, Padraic G.

doi:10.4049/jimmunol.178.7.4557

Cited by 253 publications

(248 citation statements)

References 55 publications

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“…Thus, cystatin-treated macrophages resembled type II-activated macrophages (42). Just recently it has been shown that infection with the trematode parasite S. mansoni prevents experimental colitis via a macrophage-mediated mechanism (43). We are currently studying the molecular mechanisms of immune modulation by filarial cystatin, such as the signaling pathways involved and the domains of cystatin responsible for the described effects.…”

Section: Discussionmentioning

confidence: 99%

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

Schnoeller

Rausch

Pillai

et al. 2008

The Journal of Immunology

228

196

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The coincidence between infections with parasitic worms and the reduced prevalence of allergic disease in humans and in animal models has prompted the search for helminth molecules with antiallergic and antiinflammatory potential. We report herein that filarial cystatin, a secreted protease inhibitor of filarial nematodes, suppresses Th2-related inflammation and the ensuing asthmatic disease in a murine model of OVA-induced allergic airway responsiveness. Treatment with recombinant filarial cystatin inhibited eosinophil recruitment, reduced levels of OVA-specific and total IgE, down-regulated IL-4 production, and suppressed allergic airway hyperreactivity when applied during or after sensitization and before challenge with the allergen. Depletion of macrophages by clodronate-containing liposomes prevented the curative effects and restored the levels of infiltrating cells, IgE, and allergic airway reactivity. Blocking of IL-10 by application of anti-IL-10 receptor Abs restored the reduced number of infiltrating cells and the levels of OVA-specific IgE. In contrast, depletion of regulatory T cells by anti-CD25 Abs had only limited effects. Cystatin also modulated macrophage-mediated inflammation in a murine model of dextran sulfate sodium-induced colitis, leading to reduction of inflammatory infiltrations and epithelial damage. Our data demonstrate that treatment with a single helminth protein can exert the antiallergic effects of helminth infections.

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Section: Discussionmentioning

confidence: 99%

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

Schnoeller

Rausch

Pillai

et al. 2008

The Journal of Immunology

228

196

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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.…”

mentioning

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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“…and P.J.) blinded to the time point, strain, and treatment groups, as per published methods (28,29).…”

Section: Methodsmentioning

confidence: 99%

Interleukin 37 expression protects mice from colitis

McNamee

Masterson

Jedlicka

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

297

280

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IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six-to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50% (P < 0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P < 0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1β and TNFα from ex vivo colonic explant tissue was decreased 5-and 13-fold, respectively, compared with WT (P £ 0.005), whereas IL-10 was increased sixfold (P < 0.001). However, IL-10 was not required for the anti-inflammatory effects of IL-37 because IL-10-receptor antibody blockade did not reverse IL-37-mediated protection. Mechanistically, IL-37 originating from hematopoietic cells was sufficient to exert anti-inflammatory effects because WT mice reconstituted with hIL-37tg bone marrow were protected from colitis. Thus, IL-37 emerges as key modulator of intestinal inflammation.cytokine | intestine | inflammatory bowel disease

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Infection with a Helminth Parasite Prevents Experimental Colitis via a Macrophage-Mediated Mechanism

Cited by 253 publications

References 55 publications

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages

Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta

Interleukin 37 expression protects mice from colitis

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