Tobias Martin Hohl, MD, PhD

Every time we breathe, our lungs encounter a variety of airborne microbes, such as viruses and fungi. A key question is how the immune system manages infections with different types of microbes at the same time. During the recent pandemic, secondary fungal infections became a major issue for patients with severe COVID-19. To study this, we developed an experimental model to study immune responses during co-infection with a coronavirus and the mold Aspergillus fumigatus. We will study whether the immune response to coronaviruses affects the antifungal functions of immune cells called myeloid cells, which are critical for clearing fungal infections and ensuring survival. This research will help us better understand the immune system’s balancing act during co-infections and could lead to new treatment strategies.

The Keith R. Ayres Emerging Respiratory Pathogens Award 

Update: This project addresses the observation that patients with severe COVID-19 can develop invasive aspergillosis, a life-threatening mold infection. We also are examining how coronavirus-induced lung inflammation impacts fungal clearance in the respiratory tree. To accomplish this, we developed a pulmonary coronavirus infection in a murine hepatitis virus (MHV)–Aspergillus co-infection model. We found that MHV infection triggers natural killer cells in the lungs to produce high levels of a protein called interferon-gamma. Although interferon-gamma helps the immune system fight some infections, in this case it reduces the ability of neutrophils, white blood cells that are the body's main defense against Aspergillus, to kill the fungus. We are conducting experiments to understand how coronavirus-induced IFN-gamma impacts neutrophil genes and molecules that define their antifungal properties.