A possible new role of type I interferon (IFN)-mediated survival of influenza A virus (IAV)-infected lung cells in lung repair

Descrizione del progetto

I sopravvissuti al virus: gli artefici della guarigione polmonare

Le infezioni influenzali gravi causano danni polmonari permanenti e rappresentano una grave minaccia per la salute a livello mondiale. Sebbene il sistema immunitario di solito elimini le cellule infette, alcune cellule progenitrici polmonari fondamentali, ovvero gli elementi fondamentali del processo di riparazione, sopravvivono al virus. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto RIPAIR analizzerà in che modo queste «cellule sopravvissute» contribuiscano alla rigenerazione polmonare. Avvalendosi di modelli murini all’avanguardia, organoidi polmonari umani e sequenziamento dell’RNA, il progetto RIPAIR analizzerà queste cellule per determinare in che modo favoriscono il recupero dei tessuti. Il progetto offrirà inoltre una formazione avanzata ai ricercatori e promuoverà la collaborazione internazionale. In definitiva, il progetto mira a individuare nuovi bersagli per favorire il recupero polmonare, contribuendo a prevenire l’insufficienza respiratoria cronica che si verifica quando i processi naturali di riparazione falliscono.

Obiettivo

Lower respiratory tract infections caused by influenza viruses remain a leading cause of morbidity and mortality worldwide and predispose individuals to secondary respiratory disease. Type I interferon (IFN) protects against severe disease by blocking or restricting viral replication before the immune system clears those infected cells. However, a new concept has emerged from studies done in mice, suggesting that a significant proportion of lung progenitor cells survive influenza A virus (IAV) infection in an IFN-dependent manner without clearance. The RIPAIR project will investigate the relevance and function of these IAV-survivor cells in lung repair, by studying if (i) a specific innate immune response in progenitor cells mediates their preferential resistance to IAV, (ii) these surviving progenitor cells enhance the lung's ability to regenerate, and (iii) these survivor progenitor cells are also present in human lung tissue after IAV infection, where they contribute to tissue repair. Understanding these mechanisms is critical as failing repair might negatively impact cell survival (“RIP air”).
This project combines the expertise of an aspiring young researcher trained in viral immunopathogenesis with that of an experienced host specialized in IAV biology and long-term RNA virus consequences. Using state-of-the-art mouse and human lung organoid systems, genetically engineered in vivo models, and unbiased RNA sequencing, RIPAIR will visualize and functionally characterize survivor progenitor cells to uncover if and how they contribute to tissue recovery, both in an animal and human model. In the long term, this basic research project may inspire new directions for identifying targets that support lung recovery after IAV infection. Simultaneously, RIPAIR will provide advanced training in cutting-edge methodologies, foster interdisciplinary collaboration, and strengthen the fellow’s career development within an international and stimulating research environment.