Post-infectious immune reprogramming and its association with persistence and chronicity of respiratory allergic diseases
Coordinator: Nikolaos G. PAPADOPOULOS
Project Number: 260895
EC contribution: € 5,991,600.00
Project website: http://www.predicta.eu
Chronic inflammatory diseases associated with allergy, including asthma and rhinitis, constitute a major and continuously growing public health concern for Europe. However, the causative factors and mechanisms converting a physiological inflammatory reaction to a chronic response triggering allergic disease remain elusive.
Viral infections, particularly those caused by human rhinoviruses (RV) are the most frequent triggers of acute asthma exacerbations. RV infections have more recently been associated with asthma initiation; there is evidence suggesting that such infections may also contribute to respiratory allergy persistence.
The strategic aims of PreDicta are to evaluate the hypothesis that repeated infections reprogram the immune system towards a persistent inflammatory pattern leading to respiratory allergies by
- dissecting the molecular and cellular mechanisms involved in the lack of resolution of inflammation in the context of a human disease,
- identifying specific infectious agents and underlying altered host-pathogen interactions, and develop relevant prognostic and therapeutic strategies.
PreDicta follows three interconnected workflows: models, mechanisms and translational output. Models include a longitudinal cohort in children, mouse models of repeated virus infection, primary epithelial cultures from patients, viral-bacterial interaction models, and models of epithelial-T-cell-dendritic cell interactions. These will be used to look into disease persistence, inflammation patterns, dysbiosis, immune regulation and resolution of inflammation. Translational outputs include prognostic use of subtype-specific antiviral antibodies, DNAZymes for therapeutic use and delivery technologies targeted to the bronchial epithelium.
This interdisciplinary Consortium with strong track record, unique resources and strong translational focus, aims to produce new knowledge and technologies that can rapidly and effectively reach clinical care.