Immune reprogramming in allergy
Millions of people are affected globally by asthma and rhinitis – allergy-related diseases caused by chronic inflammations. Despite the growing health concern, the causative factors and mechanisms triggering allergic disease remain elusive. Childhood asthma usually follows viral respiratory tract infections. The EU-funded PREDICTA (Post-infectious immune reprogramming and its association with persistence and chronicity of respiratory allergic diseases) project tested the hypothesis that such infections could re-programme the immune system and predispose individuals towards chronic inflammation. They aimed to understand the pathogenesis of respiratory allergies and to suggest new preventive and innovative treatment strategies. Viral infections, particularly those caused by human rhinoviruses (RVs) are the most frequent triggers of acute asthma. In an ex vivo model of interactions between RVs and bacterial (Staphylococcus Aureus) infections, scientists have found that consecutive infection by these pathogens causes acute inflammation. Interestingly, the immune response during an asthma attack was different depending on the trigger: a virus or an allergen. RV is able to enter monocytes and B-cells, activating them. The exposure of T-cells to viral and bacterial triggers breaks established tolerance through myeloid dendritic cells. Researchers found that suppressor of cytokine signalling 1 (SOCS-1), a factor controlling interferon, is overexpressed in asthma, providing a possible target for intervention. They also determined that cytokines produced by the epithelium (IL25 and IL33) can drive allergic immune responses in the lung. Project partners established a new method to measure lipid factors that influence the resolution of inflammation. In children, lipid mediators were depleted in serum after an acute exacerbation and recovery was slow. Administration of lipid mediators – Protectin D1 and Resolvin D1, significantly reduced inflammation. Translational output of PREDICTA included creation of a peptide chip for identification of antibody responses to different RV subtypes. Importantly, partners designed antisense molecules, DNAzymes, which could cleave RV in-vitro. These could prove to be excellent anti-RV agents. The PREDICTA consortium with its strong track record, unique resources and translational focus accumulated new knowledge and developed clinically relevant technologies. These tools should aid in further elucidating asthma and rhinitis for better disease prevention programmes.
Keywords
Immune reprogramming, allergy, chronic inflammation, infection, PREDICTA, DNAzymes
