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SCHISTOINIR


Helminth diseases Projects

Innate Immune Responses and Immunoregulation in Schistosomiasis: Novel mechanisms in the control of infection and disease

Project Number
: 032405
Duration
: 48 months
EC contribution
: € 2,000,000
Type
: Specific Targeted Research Projects (STREPs) and Coordination Actions (CAs) for Developing countries (DEV)
Diseases
: Helminth diseases
Starting date
: 01/11/2006

Summary:

Schistosomiasis is an important parasitic disease in the developing world and is largely chronic in nature. Helminth infections, such as Schistosoma sp., often cause down-regulation of the adaptive immune response possibly through long-term, or repeated stimulation of the innate immune system following binding of parasite molecules to a limited number of innate receptors (e.g. Toll-like receptors). This aspect of the immune system represents a novel route to exploit in future control programs.

Therefore, our proposal has four objectives.

  1. We will investigate differences in the innate immune response, specifically of innate receptors in groups of individuals with different histories of infection and extent of pathology, which will be further dissected in models of infection.
  2. Glycan structures on molecules released by schistosomes are important candidate ligands of host innate receptors and so will be characterised, isolated and synthesised.
  3. Isolated molecules will be tested using human in vitro assays and in vivo model systems, to identify those molecules with the greatest capacity to enhance or regulate immune responsiveness. These molecules bear promise as potential adjuvants in drug and vaccine control programmes, or as therapeutics to control pathology.
  4. Finally, Geographical Information Systems will be applied to link features of the innate immune response to the history of exposure, and expression of pathology.

This framework will facilitate the implementation of drug and vaccine control programmes to those most at risk. The proposal is based upon a multidisciplinary and integrated consortium bringing together field based researchers (epidemiologists, health care workers), statisticians, and basic scientists (immunologists, biochemists) from 3 African and 3 European countries.
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