ovalbumin and Helminthiasis--Animal

The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; B-Lymphocytes; Bone Marrow; Calcitriol; Female; Helminthiasis, Animal; Immunoglobulin Class Switching; Immunoglobulin E; Immunoglobulin G; Intestinal Diseases, Parasitic; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Nematospiroides dubius; Organ Specificity; Ovalbumin; Receptors, Calcitriol; Spleen; T-Lymphocytes; Vitamin D Deficiency

Epidemiological studies suggest that infections with helminths protect from the development of asthma. Supporting this view is our published finding that infection with Nippostrongylus brasiliensis decreased ovalbumin-induced Th2 responses in the lung of mice.. To evaluate if N. brasiliensis excretory-secretory products also prevent the development of asthma.. Mice were immunized with ovalbumin/alum intraperitoneally in the absence or presence of helminthic products and then challenged intranasally with ovalbumin. Six days later, we analyzed if the mice developed Th2 responses in the lung.. The application of the helminthic products together with ovalbumin/alum during the sensitization period totally inhibited the development of eosinophilia and goblet cell metaplasia in the airways and also strongly reduced the development of airway hyperreactivity. Allergen-specific IgG1 and IgE serum levels were also strongly reduced. These findings correlated with decreased levels of IL-4 and IL-5 in the airways in product-treated animals. The suppressive effects on the development of allergic responses were independent of the presence of Toll-like receptors 2 and 4, IFN-gamma, and most important, IL-10. Interestingly, suppression was still observed when the helminthic products were heated or treated with proteinase K. Paradoxically, we found that strong helminth product-specific Th2 responses were induced in parallel with the inhibition of ovalbumin-specific responses.. Our results suggest that helminths suppress the development of asthma by secreting substances that modulate allergic responses without affecting the generation of helminth-specific Th2 immunity. The identification of these products may lead to the design of novel therapeutic intervention strategies for the treatment of asthma.

Topics: Animals; Bronchial Provocation Tests; Endopeptidase K; Female; Goblet Cells; Helminthiasis, Animal; Immunoglobulin E; Immunoglobulin G; Metaplasia; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Nippostrongylus; Ovalbumin; Pulmonary Eosinophilia; Respiratory Hypersensitivity; Th2 Cells

It has been proposed that infections with helminths can protect from the development of allergic diseases. However, epidemiological and experimental studies have yielded conflicting results. Therefore we investigated if an infection with Nippostrongylus brasiliensis influenced the development of allergen-induced Th2 cell responses in mice. We found a decrease in allergen-induced airway eosinophilia and Eotaxin levels in the airways when mice were infected with the helminths 8 weeks, and especially 4 weeks, but not 1 or 2 weeks before ovalbumin (OVA)-airway challenge. While OVA-specific IgG1 and IgE serum levels and cutaneous hypersensitivity reactions were not reduced by the helminth infection, there was a reduction in OVA-specific IgG1 and IgE levels in bronchoalveolar lavage fluid of mice. Suppression of allergen-induced airway eosinophilia and reduction of Eotaxin production was not observed in IL-10 deficient mice. In addition, we found that helminth-induced airway eosinophilia and Eotaxin production was strongly increased in IL-10 deficient mice infected with the helminths in comparison to control mice. Taken together, these results show that infection with N. brasiliensis suppresses the development of allergen-induced airway eosinophilia and that this effect may be mediated by IL-10. Our results support the view that helminth infections can contribute to the suppression of allergies in humans.

Topics: Allergens; Anaphylaxis; Animals; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Cell Count; Cells, Cultured; Chemokine CCL11; Chemokines, CC; Eosinophils; Helminthiasis, Animal; Immunoglobulin E; Immunoglobulin G; Inflammation; Interferon-gamma; Interleukin-10; Interleukins; Lymph Nodes; Macrophages, Alveolar; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Nippostrongylus; Ovalbumin; Respiratory Hypersensitivity; Respiratory System; Skin Tests; Spleen; Th2 Cells; Vaccination