Abstract
S. aureus is a leading cause of bacterial infection. Macrophages, the first line of defence in the human immune response, phagocytose and kill S. aureus but the pathogen can evade these responses. Therefore, the exact role of macrophages is incompletely defined. We develop a mathematical model of macrophage - S. aureus dynamics, built on recent experimental data. We demonstrate that, while macrophages may not clear infection, they significantly delay its growth and potentially buy time for recruitment of further cells. We find that macrophage killing is a major obstacle to controlling infection and ingestion capacity also limits the response. We find bistability such that the infection can be limited at low doses. Our combination of experimental data, mathematical analysis and model fitting provide important insights in to the early stages of S. aureus infections, showing macrophages play an important role limiting bacterial replication but can be overwhelmed with large inocula.
Highlights
S. aureus is a major cause of both community-acquired and hospital-acquired infections, causing a broad spectrum of disease ranging from skin and soft tissue infections to bacteraemia and infection of prosthetic devices (Cole et al, 2014)
We have recently demonstrated that differentiated macrophages, that model tissue macrophages such as the alveolar macrophage resident in the lung, competent for bacterial clearance, have a finite capacity for intracellular killing, which is the rate limiting step in pathogen clearance (Jubrail et al, 2015 )
Mathematical model We model the interaction between macrophages and S. aureus using a set of ordinary differential equations as described below
Summary
S. aureus is a major cause of both community-acquired and hospital-acquired infections, causing a broad spectrum of disease ranging from skin and soft tissue infections to bacteraemia and infection of prosthetic devices (Cole et al, 2014). The pathogen contributes significantly to infection-related mortality and healthassociated costs (de Kraker et al, 2011). Part of its success stems from a range of pathogen adaptations that subvert host defence (Cole et al, 2014). Macrophages are the resident phagocytes in tissues and play critical roles in host defense as the first professional phagocyte to encounter bacteria at sites of infection (Dockrell et al, 2003). S. aureus has been classified as an extracellular bac-
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