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Project C02

Metabolic control of innate and adaptive immune responses to cutaneous Staphylococcus aureus infection

Dr. Martin Vaeth


Glucose is the universal fuel for both pathogens and immune cells of the host. The competition for glucose and other nutrients, low oxygen levels and acidosis at the site of infection represent major metabolic challenges for immune cells to contain and eliminate invading pathogens. Moreover, microbes actively deprive essential nutrients, including glucose, to modulate and suppress immune responses. Staphylococcus aureus is a dormant pathobiont that colonises the skin of healthy individuals asymptomatically but can cause severe skin and soft tissue infections when the skin barrier is impaired and/or the immunity of the host is compromised. S. aureus differs from other skin-colonising staphylococci not only by virulence factors, but also by its metabolic adaption to anaerobic environments. These adaptations include high expression of carbohydrate transporters to compete for glucose, increased glycolysis, and lactate production. Both nutrient depletion and acidosis attenuate immune responses to the pathogen and promote the dissemination of the pathogen. The activation of antigen-specific T cells is characterised by a “glycolytic switch” which supports clonal expansion of these cells and their effector differentiation. Similarly, neutrophils depend on glycolysis for their anti-bacterial effector function. In this project, we will investigate how the metabolic competition between immune cells of the host and S. aureus shapes local immunity and how glucose uptake mechanisms of innate and adaptive immune cells prevent the spreading of the pathogen to secondary infection sites. We hypothesise that the metabolic and epigenetic reprogramming of T cells and neutrophils is relevant for determining local immunity and systemic protection from S. aureus infections and aim to characterise decision points governing this reprogramming.

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