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Neutrophil oxidants in infection and inflammation

65 months
Approved budget:
Professor Mark Hampton
Health issue:
Infectious disease
Proposal type:
Lay summary
Neutrophils are abundant white blood cells that defend us against pathogenic bacteria. Fatal infections occur when neutrophils are overwhelmed or bacteria evade them. When unrestrained during inflammation, neutrophils damage healthy tissue. Aberrant neutrophil activity occurs in many diseases, including pneumonia, arthritis, and heart disease. Neutrophil behaviour is often linked to their ability to produce reactive oxidants. Our objective is to characterise neutrophil functions involving reactive oxidants that could be targeted for therapeutic intervention. We aim to (1) establish how neutrophils kill and digest bacteria, and how pathogenic bacteria survive the onslaught of oxidants; (2) clarify the mechanisms neutrophils use to cast out their DNA to trap extracellular bacteria, and die by pathways that resolve or exacerbate inflammation; and (3) identify biomarkers of neutrophil activity for tracking infections and inflammation during pneumonia. Our long-term goal is to advance the diagnosis and treatment of inflammatory diseases dominated by neutrophils.