Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness.

School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.
The Journal of Immunology (Impact Factor: 5.36). 02/2006; 176(1):138-47. DOI: 10.4049/jimmunol.176.1.138
Source: PubMed

ABSTRACT It has been shown that the presence of certain helminth infections in humans, including schistosomes, may reduce the propensity to develop allergies in infected populations. Using a mouse model of schistosome worm vs worm + egg infection, our objective was to dissect the mechanisms underlying the inverse relationship between helminth infections and allergies. We have demonstrated that conventional Schistosoma mansoni egg-laying male and female worm infection of mice exacerbates airway hyperresponsiveness. In contrast, mice infected with only schistosome male worms, precluding egg production, were protected from OVA-induced airway hyperresponsiveness. Worm-infected mice developed a novel modified type 2 cytokine response in the lungs, with elevated allergen-specific IL-4 and IL-13 but reduced IL-5, and increased IL-10. Although schistosome worm-only infection is a laboratory model, these data illustrate the complexity of schistosome modulation of host immunity by the worm vs egg stages of this helminth, with the potential of infections to aggravate or suppress allergic pulmonary inflammation. Thus, infection of mice with a human parasitic worm can result in reduced airway inflammation in response to a model allergen.

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    ABSTRACT: Background Cystic echinococcosis (CE) is a near cosmopolitan zoonosis caused by the larval stage of the dog tapeworm Echinococcus granulosus. E. granulosus infection induces a polarized T-helper type 2 (Th2) systematic immune response in its intermediate hosts. However, it is not known whether the infection modulates lung inflammation by regulating local immune response. In this study, we examined the effects of E. granulosus infection on mouse ovalbumin (OVA)-induced asthma model.MethodsBALB/c mice were intraperitoneally transplanted with 50 small E. granulosus cysts cultured in vitro. At 3 months post-inoculation, the mice were sensitized and challenged with ovalbumin (OVA). For histopathological studies, hematoxylin eosin and periodic acid schiff staining was used to examine the inflammatory cells infiltration and goblet cells hyperplasia, respectively. Cytokine levels were measured by mouse cytometric bead array (CBA) Kit and quantitative RT-PCR and other molecular biological approaches. Airway hyperresponsiveness was assessed in response to increasing doses of methacholine. Serum immunoglobulins were determined by ELISA.Results E. granulosus infection significantly increased Th2 and Treg cytokine levels in serum and lung tissues, but down-regulated the expression of IL-5 in the lungs and IL-17A in serum and lung tissues of asthmatic mice sensitized and challenged with OVA. Histological staining of lung tissues showed that E. granulosus infection significantly reduced the severity of OVA-induced airway inflammation including reduction of eosinophil cell infiltration and mucus production. The E. granulosus infection also reduced eosinophil accumulation induced by OVA in bronchoalveolar lavage fluid (BALF) and also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma.Conclusions E. granulosus infection remarkably reduces the severity of OVA-induced airway inflammation likely through enhancing IL-10 and down-regulation of IL-5 and IL-17A .
    Parasites & Vectors 11/2014; 7(1):522. DOI:10.1186/PREACCEPT-5653772041390381 · 3.25 Impact Factor
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    ABSTRACT: Helminth infections are associated with decreased rates of autoimmunity and allergy, and several clinical studies have demonstrated that intentional infection with helminths can reduce symptoms of autoimmune diseases. In contrast, though numerous animal studies have demonstrated that helminth infections ameliorate allergic diseases, clinical trials in humans have not shown benefit. In this article, we review in detail the 2 human studies that have prospectively tested whether helminth infections protect against allergy. We next review the research designs and results obtained from animal studies, and compare these to the human trials. We then postulate possible reasons for the lack of efficacy observed in clinical trials to date and discuss potential future areas of research in this field.
    Journal of Allergy and Clinical Immunology 08/2014; 135(2). DOI:10.1016/j.jaci.2014.07.007 · 11.25 Impact Factor
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    ABSTRACT: Allergic airway disease is a major global health burden, and novel treatment options are urgently needed. Numerous epidemiological and experimental studies suggest that certain helminths and bacteria protect against respiratory allergies. These microorganisms are strong regulators of the immune system, and various potential regulatory mechanisms by which they protect against allergic airway inflammation have been proposed. Whereas early studies addressed the beneficial effect of natural infections, the focus now shifts toward identifying the dominant protective molecules and exploring their efficacy in models of allergic airway disease. In this article, we will review the evidence for microbe-mediated protection from allergic airway disease, the potential modes of action involved and discuss advances as well as limitations in the translation of this knowledge into novel treatment strategies against allergic airway disease.
    Expert Review of Respiratory Medicine 08/2014; DOI:10.1586/17476348.2014.949244

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