Oxygen deprivation heightens risk of illness by changing genes

Scientists found that oxygen deprivation – known as hypoxia – changes the genetic material of immune cells called neutrophils, reducing their capacity to destroy harmful microbes.

The team discovered that low oxygen appears to leave a lasting mark on the bone marrow cells that produce neutrophils, meaning the impact can persist after oxygen levels return to normal.

The findings may help explain why people recovering from conditions that lower oxygen levels, such as severe lung disease, are more vulnerable to repeated infections, experts say.

Researchers from the University of Edinburgh now plan to investigate what triggers these long-term changes and whether they can be reversed to boost the body’s defence against infection.

Neutrophils are one of the body’s first lines of defence, rapidly targeting and destroying invading microbes. Their activity must be precisely balanced – they need to be strong enough to fight infection but not so strong that they harm healthy tissues.

Researchers studied neutrophils from patients recovering from acute respiratory distress syndrome (ARDS) and from healthy volunteers recently exposed to high-altitude, low-oxygen environments.

They found that low oxygen led to changes in the way the cells’ DNA was packaged, altering how the neutrophils behaved. The same modifications were also found in bone marrow precursor cells that produce neutrophils.

These cells underwent a process known as histone clipping – a change to proteins that helps organise DNA – which can alter how genes are switched on or off.

Experts say this discovery suggests that low oxygen can reprogramme the immune system, leaving a lasting imprint that affects how new immune cells respond in the future.

The study is published in the journal Nature Immunology.

It was funded by Wellcome and the UKRI NIHR UK Coronavirus Immunology Consortium.

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Centre for Inflammation Research

Institute of Regeneration and Repair

Walmsley lab