Hypoxia weakens the body's infection defense by changing genetic material of neutrophils

Low oxygen levels in the blood can alter the genetic makeup of key immune cells, weakening the body's ability to fight infection, new research shows. 

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 defense against infection. 

Neutrophils are one of the body's first lines of defense, 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. 

Recognizing that low oxygen levels have a long-lasting effect on how early responder immune cells read their genetic code is important because it explains why these cells are less good at controlling infection many months after a severe respiratory illness. The discovering opens up new ways to think about treating long-term immune dysfunction and improve infection defenses."

Manuel Alejandro Sanchez Garcia, Postdoctoral Research Fellow, University of Edinburgh's Centre for Inflammation Research

The study is published in the journal Nature Immunology: https://www.nature.com/articles/s41590-025-02301-9 [URL will be live once embargo has lifted]. It was funded by Wellcome and the UKRI NIHR UK Coronavirus Immunology Consortium.