Infection of the lower respiratory tract (LRTI) are still associated with high morbidity and mortality, highlighting the utmost need for novel therapeutic options. In fact, several pathogens can cause LRTI and the current COVID-19 pandemic underlines the importance/thread of viral pathogens. Despite viral intruders, also bacterial and mycobacteria can cause a variety of life-threatening infections, which can be become hard to treat, if the respective pathogen is resistant to the current standard of care such as antibiotics. Of note, alveolar macrophages in the lung are the most abundant cell type in the bronchioalveolar space, able to sense and to clear various types of intruders. Recent knowledge in the biology of macrophages and in particular alveolar macrophages is pointing towards a strong therapeutic potential of these cells. In the past decade, alveolar macrophages have been associated with the onset and progression of a variety of lung diseases incl. pulmonary infections. Given the important role of macrophages in (myco)bacterial infections and recent innovations in the field of regenerative medicine, the iPSC2Therapy proposal will apply the technology of induced pluripotent stem cell (iPSC) technology to elaborate the anti-mycobacterial properties of iPSC-derived macrophages, all directed towards the development of novel cell-based immunotherapies targeting bacterial airway infections. This ambitious aim is combined with seminal insights into the developmental trajectories of human macrophages, with the overall goal to improve current macrophage-manufacturing pipelines and to generate macrophage-cell products which show a therapeutic effect upon intra-pulmonary transplantation. Overall, the work of iPSC2Therapy lays the foundation for new cell-based immunotherapies for the lung and other tissues with direct impact for patients suffering from mycobacterial lung infections and beyond.
