Heat inactivated thenthereby Listeria monocytogenes, which was given as an adjuvant together with an allergen, activated mature CD8 plasmacytoid DCs to produce IL 10 and IL 12, resulting in development of IL 10 and IFN c producing allergen specific Tregs. These Th1 like Tregs expressed Foxp3 and later prevented allergen mediated airway hyperreactivity in mice. 63 Modulation of Immune Responses by Parasites During their acute infectious state, helminthes secrete proteases that act as virulent factors and induce a strong Th2 immune response and a massive unspecific IgE production in the host. Further, proteases act as danger signals and activate DCs that might promote allergen sensitization. 64 Additionally, parasite antigens such as tropomyosins might show cross reactivity with allergens, resulting in enhanced allergen sensitization.
65 In contrast, the anti inflammatory effects of helminthes in the chronic Inhibitors,Modulators,Libraries state might be responsible for inverse correlations between parasitic and allergic diseases. 66 The Inhibitors,Modulators,Libraries anti inflammatory property of helminthes is more and more Inhibitors,Modulators,Libraries used for immunomodulatory therapeutic and prevention concepts, although Inhibitors,Modulators,Libraries the underlying mechanisms have not been clarified. Both DCs and APCs, as well as CD4 T cells, might play a key role. According to experimental data, helminthes induce Foxp3 IL 10 and TGF b producing Tregs that inhibit development of allergen mediated sensitization and airway inflammation in mice. 67,68 Helminthes also induce CD1 natural killer T cells, a subgroup of T cells that express natural killer cell markers and produce immunoregulatory cytokines.
69 Filarias produce the anti inflammatory molecule ES62, which suppresses B cell activation and proliferation by interaction with the signal transduction cascade of the B cell antigen receptor and inhibits Inhibitors,Modulators,Libraries production of proinflamma tory cytokines by interaction with the TLR signal transduc tion cascade. 70 Further, oligosaccharides with immunomodulatory capacities such as lacto N neotetraose, which helminthes express on their surface, induce a subgroup of natural Gr1CD11bF480 suppressor cells, immature myeloid cells that produce IL 10 and TGF b and more inhibit proliferation of naive CD4 T cells via IFN c dependent cellcell contact. 71 Development of derivatives of these natural immunomodulatory molecules might be of use for primary prevention against allergen mediated diseases. Conclusion Enormous progress in clarifying the genetic and molecular mechanisms of allergic sensitization allows the develop ment of novel immunomodulatory strategies aimed at primary prevention of allergen mediated diseases. These are based either on the inhibition of their most relevant pathogenetic elements or in the induction of natural immunoregulatory mechanisms.