Einfluss eines Nematodenimmunomodulators und einer Nematodeninfektion auf zwei Allergiemodelle

Influence of a nematode immunomodulator and a nematode infection on two models of allergic disease Parasitic worms, like filariae, have the intriguing capacity to modulate immune responses directed against them, and therefore can persist up to years in a host. This immunomodulation does not only protect the parasite but was found to mediate a negative correlation between infections with parasitic worms and the prevalence of allergic disease. Secreted molecules of the parasites were found to be strongly involved in immune deviation and might bear themselves strong anti-allergic and anti-inflammatory potential. In the present study filarial cystatin, a secreted protease inhibitor of the filarial nematode Acanthocheilonema viteae, was found to suppress Th2-related inflammation and the ensuing asthmatic disease in a murine model of ovalbumin-induced allergic airway responsiveness. Treatment with recombinant filarial cystatin during or after sensitization and before challenging mice with the allergen, inhibited airway inflammation and airway hyperreactivity, reduced levels of allergen-specific IgE and down-regulated IL-4 production. These effects of Av17 on allergic airway inflammation were probably due to induction of IL-10 secreting macrophages. Depletion of macrophages by liposomes containing clodronate as well as blocking of IL-10 by application of anti-IL-10 receptor antibodies, prevented the curative effects and restored allergic airway inflammation. In contrast, depletion of regulatory T cells by anti-CD25 antibodies had only limited effects. Treatment with cystatin in a model of allergic skin disease, namely ovalbumin-induced dermatitis, was determined to have suppressive activity on inflammation and the ensuing allergic disease, too. Eczema formation and recruitment of inflammatory cells to lesions was clearly impaired and also allergen-specific IgE production substantially reduced. The protective effect on atopic dermatitis was accompanied by a dramatic increase of TGF-ȕ in the eczema region. Hence, the data demonstrate that treatment with a single recombinant helminth protein can exert the anti-allergic effects of helminth infections. Another part of this study was to investigate if immunomodulation by helminths is dependent on the biology (localisation) of the worm. The influence of a gastrointestinal nematode infection with Heligmosomoides polygyrus, was analyzed in two distinct murine models of allergy: mucosa-associated airway disease and non-mucosal, cutaneous atopic dermatitis. Mice concomitantly infected with H. polygyrus clearly showed reduced signs of allergic airway inflammation. In contrast, no significant differences in phenotypical signs of 6 Zusammenfassung-Summary dermatitis, such as severity of eczematous skin lesions, were observed between infected and control animals in the atopic dermatitis model. Worm infection was associated with significantly elevated …