Decode VirAttacks

Sources of funding

Welbio Advanced Grant (350 k€ / year)

Summary

Acute exacerbations of chronic airway diseases such as asthma or COPD represent a huge socio-economic burden for healthcare systems. They are frequently triggered by respiratory viral infections, are not well controlled by standard therapies and are associated with poor disease outcomes. Hence, understanding the mechanisms underlying ‘viral-triggered exacerbations of chronic airway diseases’, called ‘VirAttacks’, is of fundamental biological importance and an urgent need to identify novel biology, biomarkers, pathways and therapeutic targets. We have previously identified neutrophil extracellular traps (NETs) as important host triggers of rhinovirus-induced asthma exacerbations, and our unpublished observations point towards an underappreciated functional diversity and plasticity of lung myeloid cells after viral infection that can have important implications for VirAttacks and need to be investigated further. Here, we postulate that, in asthmatic or COPD subjects, virally infected epithelial cells (ECs) closely interact with distinct myeloid cell subpopulations to shape their identity and orchestrate key pathological features of VirAttacks such as EC damage and impaired repair, unresolved inflammation and defective host defense. DECODE VirAttacks is an ambitious and innovative translational research program aiming at investigating in-depth the bidirectional crosstalk between ECs and myeloid cells during VirAttacks. To this end, we will employ relevant mouse asthma and COPD models and human ex vivo models in combination with innovative tools and integrative technologies. In parallel, we will collect and analyze clinically relevant human samples from exacerbation-prone asthma and COPD patients. We expect to reveal key novel cellular and molecular mechanisms of VirAttacks in asthma and COPD with the objective to identify novel biomarkers of disease risk and severity, and to contribute to personalized medicine approaches based on treatable traits.