Staphylococcus aureus (S. aureus) is a major cause of human death and disease but the factors that determine the outcome of this host-pathogen interaction are still poorly understood. Both bacterial colonisation and immune cell infiltration induce local tissue hypoxia; sites of infection are characterized by profound hypoxia, which may exert a dramatic effect on host-pathogen interactions. It has been shown that hypoxia impairs the ability of neutrophils to kill intracellular S. aureus but promotes the extracellular release of a range of anti-Staphylococcal proteins. Other immune cells such as Kupffer cells are key in determining whether S. aureus infection becomes disseminated, but the impact of hypoxia on these cell populations is unknown. We hypothesise that tissue hypoxia is a key determinant of the outcome of these host-pathogen interactions. The project will aim to explore this hypothesis, using primary human phagocytes derived from the peripheral blood of healthy volunteers or mouse liver. Hypoxia (3-12 KPa) will be delivered using a Ruskinn SciTive hypoxic workstation. |
The Team
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