Ziel
The hygiene hypothesis postulating the paradoxical protective role of infections on immune-mediated
diseases including atopy (i.e. atopic dermatitis, rhinitis, asthma) and more recently autoimmune diseases has
been the matter of extensive investigation. The aim of the present project is to validate this hypothesis
integrating epidemiological and experimental studies.
We will review in a meta-analysis published studies of direct and indirect markers of infections and atopic
diseases, and conduct a case-control study to analyse the association between infections and atopy using
atopic dermatitis as a prototypic model. This epidemiological study will assess the occurrence of different
infections and other risk factors related to the incidence of atopic dermatitis in children under age five in
Italy (300 cases and 600 controls).
This epidemiological study will be supported by experimental approaches addressing mechanistic questions
raised by the hygiene hypothesis. Experimental models will include induction of acute and chronic
bronchoconstriction/asthma, atopic dermatitis. In addition the project will aim at devising new mouse models
of atopy. The nature of infections providing protection against allergic diseases will be investigated to
characterise the difference at the molecular level between protective and non protective pathogens or their
derivatives. The underlying immune mechanisms notably homeostasis imbalance, antigenic competition,
stimulation of regulatory immune cells and Toll-like receptor involvement will be analysed. In addition to
developing integrated in vivo models, including the use of transgenic animals, efforts will be focussed on the
study of available synthetic pathogen-derived compounds showing a protective activity to better approach
their cellular and molecular mode of action. These studies may pave the way to novel and safe therapies that
could advantageously substitute for the “protective” immune stimulation induced by major infections.
Wissenschaftliches Gebiet
Aufforderung zur Vorschlagseinreichung
ERC-2009-AdG
Andere Projekte für diesen Aufruf anzeigen
Finanzierungsplan
ERC-AG - ERC Advanced GrantGastgebende Einrichtung
75654 Paris
Frankreich