Harnessing neutrophil biology to develop new weapons against severe mycoses

The innate immune system, and foremost neutrophils, shield us from invasive and disseminated infections caused by fungal organisms.

However, in today’s health care severe mycoses remain challenging, since both diagnostic tools and therapy options are lacking behind.

To overcome this dilemma, we need better understanding of the intricate host-pathogen interaction to be able to identify new approaches for better diagnosis and therapy.

Here, we aim to study how the most common fungal pathogen Candida albicans escapes neutrophil attack by using the toxin candidalysin.

To understand the effect of candidalysin on neutrophils, we will use sophisticated image-based techniques and biochemical tools to unravel the underlying mechanisms.

On the host side, we will delineate how neutrophils snatch micronutrients from C. albicans to render the pathogen more susceptible for subsequent phagocytosis and extracellular DNA trap killing. For the meticulous analysis we will establish a genetically tractable neutrophil cell line.

Finally, we aim to understand Candida-neutrophil interplay under physiological conditions, namely in an oxygen-limiting environment.

We will use transcriptomics and metabolomics approaches for a broad overview to allow follow-up studies of relevant signalling pathways.

Take together, our project will increase knowledge about fungal pathogenicity and immune responses with the ultimate goal to provide a basis for the development of better diagnostics and therapeutics.