Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 22, Pages -Publisher
MDPI
DOI: 10.3390/ijms20225561
Keywords
neutrophils; host-pathogen interaction; hypoxia; Staphylococcus aureus
Funding
- Florey Institute
- Medical Research Foundation
- British Lung Foundation [PPRG16-13]
- MRC MR [2995X/1]
- MRC [MR/M012328/2, MR/N02995X/1] Funding Source: UKRI
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Neutrophils are key to host defence, and impaired neutrophil function predisposes to infection with an array of pathogens, with Staphylococcus aureus a common and sometimes life-threatening problem in this setting. Both infiltrating immune cells and replicating bacteria consume oxygen, contributing to the profound tissue hypoxia that characterises sites of infection. Hypoxia in turn has a dramatic effect on both neutrophil bactericidal function and the properties of S. aureus, including the production of virulence factors. Hypoxia thereby shapes the host-pathogen interaction and the progression of infection, for example promoting intracellular bacterial persistence, enabling local tissue destruction with the formation of an encaging abscess capsule, and facilitating the establishment and propagation of bacterial biofilms which block the access of host immune cells. Elucidating the molecular mechanisms underlying host-pathogen interactions in the setting of hypoxia will enable better understanding of persistent and recalcitrant infections due to S. aureus and may uncover novel therapeutic targets and strategies.
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