Acute lower respiratory tract infections represent an increasing public health problem worldwide, and result in a disease burden greater than that of any other infection, with mortality rates unchanged over the past 50 years. Likewise, the lack of any pharmacological treatments for the most devastating clinical course of pulmonary infection, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), underscores an urgent medical need for novel, effective therapeutic approaches. Recent studies revealed that viral infection is the underlying cause of the majority of community-acquired pneumonia (CAP) among children, and in 41% of adult patients with CAP-associated ARDS. Genetic susceptibilities together with specific pre-conditions or co-morbidities are major risk factors for severe courses of respiratory viral disease, characterized by deficiencies in adequate antiviral control and/or exaggerated inflammation and tissue damage. In addition, there is increasing evidence that respiratory virus infection frequently predisposes for severe gram-positive bacterial superinfections with fatal outcome. Emergence of novel respiratory viruses such as pH1N1/2009 pandemic IV and highly pathogenic avian IV strains, or the MERS-Coronavirus which causes substantial mortality among children and adults further highlights the need for a better understanding of the underlying pathobiology.
Against this background, our research is dedicated to unraveling the mechanisms driving anti-viral host defense, to dissecting the cellular and molecular contributors to the tissue damage at the virus-host interface in the distal lung, and to defining pathways and mediators of organ regeneration in the context of viral infection, focusing on the interaction of macrophages with parenchymal cells of the distal lung and the epithelial stem cell niche. These aims will be achieved by using established in vivo virus infection models of different levels of complexity (in vitro – ex vivo – in vivo) combined with analyses of patient samples, using FACS and cell sorting (FACSCanto, LSR Fortezza, FACSAriaIII), NGS including single cell RNA-Seq, organoid modeling, and high-resolution microscopy/ life imaging techniques. The ultimate goal is to find novel disease biomarkers defining susceptibility to and recovery from lung viral attack, and to identify distinct host targets to be harnessed for novel therapeutic strategies to combat severe respiratory viral infection and associated lung injury.