Understanding and preventing NK cell-mediated lung tissue-damage upon severe respiratory viral infections

Severe respiratory viral infections are major morbidities worldwide as demonstrated by the current outbreak of SARS-CoV-2 as well as recurrent epidemics with influenza virus. Natural Killer (NK) cells are key players in the defense against virus-infected cells. However, little is known about the regulation of human NK cells in the lung, in particular during viral infections.

Here, we aim at identifying how respiratory viral infection with SARS-CoV2 or influenza virus shape NK cell characteristics in human lung (aim 1) and the regulation of lung NK cell function following in vitro infection of lung cells with SARS-CoV-2 or influenza A virus (aim 2).

The results from aim 1 and 2 will help us to harness specific lung NK cell subsets to support a targeted immune response and reducing excessive lung tissue pathology.

For this, we will collect lung tissue from deceased SARS-CoV-2- and influenza-infected patients and non-infected tissue from organ donors as well as tumor-free lung tissue from lung cancer patients.

Regulation of NK cell lung-homing and cytotoxicity will be determined by cutting edge-technologies such as 29-colour flow cytometry, RNA-seq, and live cell-imaging.

My vision is that the generated knowledge will be directly translated into development and improvement of prevention and treatment strategies for patients affected by severe respiratory viral infections of current or future epidemics.