A nematode immunomodulator suppresses grass pollen-specific allergic responses by controlling excessive Th2 inflammation

Daniłowicz-Luebert, Emilia; Steinfelder, Svenja; Kühl, Anja A.; Drozdenko, Gennadiy; Lucius, Richard; Worm, Margitta; Hamelmann, Eckard; Hartmann, Susanne

doi:10.1016/j.ijpara.2012.10.014

Cited by 50 publications

(43 citation statements)

References 65 publications

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“…Recent publications indicated the relevance of innate immune cells in immunomodulation by parasitic worms (14-16), but little is known about the target cells exploited by helminth immunomodulatory proteins or the mechanisms conferring suppression of ongoing immune responses. In previous studies, we demonstrated that AvCystatin protein administration suppresses inflammation when applied to mice in models of airway inflammation and gut inflammation (7,17). In this study, we show that the adoptive transfer of AvCystatin-modulated macrophages is sufficient to recapitulate the anti-inflammatory effects of AvCystatin, in the absence of the compound itself.…”

Section: Discussionsupporting

confidence: 53%

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Ziegler

Rausch

Steinfelder

et al. 2015

The Journal of Immunology

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Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4+ T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4+ T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact–independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.

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Section: Discussionsupporting

confidence: 53%

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Ziegler

Rausch

Steinfelder

et al. 2015

The Journal of Immunology

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“…Experimental infection of mice with gastrointestinal nematodes led to the inhibition of mucosa-associated allergic reactions [48] . When human peripheral blood mononuclear cells from allergic patients were treated with filarial cystatin, the in vitro immune response was modulated toward a Th1 profile [49] . Thus, helminthic colonization appears to provide protection or diminution of the allergic and asthmatic response, suggesting a potential function of shared antigens between parasites and environmental allergens in modulating the immune response.…”

Section: Atopy and Parasitic Infectionsmentioning

confidence: 99%

Atopy and Asthma in Migrants: The Function of Parasites

Rottem

Geller-Bernstein

Shoenfeld

2015

Int Arch Allergy Immunol

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Migration studies have shown that environmental factors in more developed and industrialized countries facilitate atopy and asthma in a time-dependent manner and are affected by age at immigration. Levels of immunoglobulin E are higher in immigrants than in the local population and gradually decrease to the levels of the general population. Parasitic infestation may function in the prevention and pathogenesis of atopic conditions in immigrants from developing countries. Helminths are associated with a reduced prevalence of clinically important atopic disorders, likely because of induction of a regulatory cell population mechanism. Improved understanding of the immunologic background of helminths and their protective function in humans has led to a growing interest in the possibility of reversal of allergies using parasites and the development of new therapies, such as immunomodulation for allergy using ova from parasites orally or intranasally. Strategies for primary prevention in high-risk atopic individuals and secondary prevention guidelines should be developed for populations in developing countries and for immigrants from developing countries to atopy-prevalent developed countries. Improved understanding of the function of parasitic infection in modulation of the immune response may lead to new therapeutic options for allergic conditions.

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“…Cystatin from the filarial nematode Acanthocheilonema viteae (AvCystatin, Av17) suppressed allergic airway hyperreactivity in mouse model of OVA-induced allergy when applied during or after sensitization before challenge with OVA [92]. More recently, Av17 was shown to suppress allergic responses in a clinically relevant mouse model of grass pollen allergy [26]. Interestingly, Av17 modulated allergen-specific responses of human PBMC derived from timothy grass pollen allergic patients [26].…”

Section: Hookwormsmentioning

confidence: 99%

“…More recently, Av17 was shown to suppress allergic responses in a clinically relevant mouse model of grass pollen allergy [26]. Interestingly, Av17 modulated allergen-specific responses of human PBMC derived from timothy grass pollen allergic patients [26]. Interestingly, another A. viteae product, ES-62 was found to supress the severity and progression of airway hyperresponiveness, as peribronchial inflammation, mucosal hyperplasia, eosinophilia and IL-4 release were markedly reduced in ES-62-treated mice in comparison to controls [69].…”

Section: Hookwormsmentioning

confidence: 99%

Allergie und Würmer: Sollen wir uns gute alte Freunde zurückholen?

Schabussova

Wiedermann

2014

Wien Med Wochenschr

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During the past 10 years, many exciting and important studies have found that certain helminth infections protect against the development of allergic diseases. Not surprisingly, several clinical trials investigated the effects of deliberate exposure to parasites like porcine whipworm (Trichuris suis) or hookworm (Necator americanus) to develop "helminth therapies". Although they proved to be a safe option to control aberrant inflammation, the final goal is to identify the parasite-derived immunnomodulatory molecules responsible for protective effects.

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A nematode immunomodulator suppresses grass pollen-specific allergic responses by controlling excessive Th2 inflammation

Cited by 50 publications

References 65 publications

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation

Atopy and Asthma in Migrants: The Function of Parasites

Allergie und Würmer: Sollen wir uns gute alte Freunde zurückholen?

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