Abstract
One third of the human population is currently infected by one or more species of parasitic helminths. Certain helminths establish long-term chronic infections resulting in a modulation of the host’s immune system with attenuated responsiveness to “bystander” antigens such as allergens or vaccines. In this study we investigated whether parasite-derived products suppress the development of allergic inflammation in a mouse model. We show that extract derived from adult male Oesophagostomum dentatum (eMOD) induced Th2 and regulatory responses in BALB/c mice. Stimulation of bone marrow-derived dendritic cells induced production of regulatory cytokines IL-10 and TGF-beta. In a mouse model of birch pollen allergy, co-administration of eMOD with sensitizing allergen Bet v 1 markedly reduced the production of allergen-specific antibodies in serum as well as IgE-dependent basophil degranulation. Furthermore, eMOD prevented the development of airway inflammation, as demonstrated by attenuation of bronchoalveolar lavages eosinophil influx, peribronchial inflammatory infiltrate, and mucus secretion in lungs and IL-4 and IL-5 levels in lung cell cultures. Reduced secretion of Th2-related cytokines by birch pollen-re-stimulated splenocytes and mesenteric lymph node cells was observed in eMOD-treated/sensitized and challenged mice in comparison to sensitized and challenged controls. The suppressive effects of eMOD were heat-stable. Immunization with model antigens in the presence of eMOD reduced production of antibodies to thymus-dependent but not to thymus-independent antigen, suggesting that suppression of the immune responses by eMOD was mediated by interference with antigen presenting cell or T helper cell function but did not directly suppress B cell function. In conclusion, we have shown that eMOD possesses immunomodulatory properties and that heat-stable factors in eMOD are responsible for the dramatic suppression of allergic responses in a mouse model of type I allergy. The identification and characterization of parasite-derived immune-modulating molecules might have potential for designing novel prophylactic/therapeutic strategies for immune-mediated diseases.
Highlights
Infections with helminth parasites represent a global health problem with more than one billion people infected worldwide
To analyze whether BALB/c mice can be primed in vivo to mount specific humoral and cellular immune responses to O. dentatum, mice were immunized twice, 10 days apart, with the crude extract of male O. dentatum in alum or with PBS in alum
We found that IL-4, IL-5 and IL10 were all suppressed in both birch pollen extract stimulated spleen (Fig. 6 A–C) and mesenteric lymph nodes (MLN) (Fig. 6 D–F) cultures derived from extract derived from adult male Oesophagostomum dentatum (eMOD)-treated mice in comparison to controls
Summary
Infections with helminth parasites represent a global health problem with more than one billion people infected worldwide. Exposure to helminth parasites has a major impact on the development and reactivity of the host’s immune system. In order to prevent their expulsion or reduce severe pathology, helminth parasites engage complex mechanisms to ‘‘act the innocent’’ in order to avoid attention and/or to actively manipulate the effector mechanism of the host immune system [1]. Even though they have common immunological features (elevated levels of IgE, eosinophilia, and production of Th2 cytokines such as IL-4 and IL-5), epidemiological studies revealed an inverse relationship between helminth infections and allergic diseases. Due to the fact that T. suis, the pig whipworm, is likely to be non-pathogenic in human subjects, the majority of reported clinical trials have been performed with this parasite
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