Helminth infections are among the most neglected communicable diseases afflicting developing countries. Pharmacological treatments are compromised by rapid re-infection, variable compliance, and emerging resistance. Vaccination has not yet succeeded in evoking strong resistance. The critical barrier in helminth control remains the failure of the immune system to clear parasites despite antigen recognition. Addressing the fundamental question of why the immune system is restrained from killing parasites, will offer a novel route for intervention to achieve an immunological cure.
Recent developments in immunology offer a conceptual framework to understand the failure of immunity and suggest how to restore the full potential of our defence mechanisms. In this model, parasites induce regulatory T cell populations, which suppress anti-parasite effector cells, as part of the parasites own strategy for survival in the host. Because regulatory T cells are stimulated by parasite antigens, repeated infection or vaccination will induce a modest immune response, but fall short at the critical effector cell level required for parasite killing. Only by inactivating or removing the regulatory T cells can the immune response display its full capability to eliminate the parasites.
We will develop this new avenue for disease control while assessing how new treatments will be accepted by the endemic populations. Our proposal is thus one of general significance to chronic infection, as well as one that will provide specific pathways to novel treatments of human schistosomiasis, and lymphatic filariasis. These two diseases represent a massive public health problem with 300 million people infected in the world today. Intervention by ablating parasite-specific regulatory T cells in these patients will solve the specific problems of schistosomiasis and filarial diseases, while at the same time proving a principle which will be applicable to chronic infections in general.
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Funding SchemeSTREP - Specific Targeted Research Project