Low oxygen Levels Can permanently Weaken Immune Response, Study Finds
New research from the University of edinburgh reveals that low blood oxygen levels (hypoxia) can induce lasting changes to the genetic makeup of neutrophils - key immune cells responsible for fighting infection – ultimately weakening the body’s defense mechanisms. The study, published in Nature Immunology, demonstrates that these changes can persist even after oxygen levels are restored.
Scientists discovered that hypoxia alters how DNA is packaged within neutrophils, impacting their ability to effectively destroy harmful microbes. Critically,the research shows the impact isn’t limited to existing neutrophils; low oxygen also appears to leave a lasting mark on the bone marrow cells that produce these cells. This suggests a prolonged vulnerability to infection following periods of oxygen deprivation.
researchers studied neutrophils from two groups: patients recovering from acute respiratory distress syndrome (ARDS) and healthy volunteers exposed to the low-oxygen environments of high altitude. They found that in both groups, low oxygen triggered a process called “histone clipping” – a modification to proteins that organize DNA – which altered gene expression. This change in how genes are switched on or off ultimately affected neutrophil behavior.
“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,” explains Manuel Alejandro Sanchez Garcia, Postdoctoral Research Fellow at the University of Edinburgh’s Center for Inflammation Research. “The discovering opens up new ways to think about treating long-term immune dysfunction and improve infection defenses.”
The findings may explain the increased susceptibility to repeated infections observed in individuals recovering from conditions like severe lung disease. The research team now plans to investigate the triggers behind these long-term changes and explore potential methods to reverse them, bolstering the body’s immune defenses.
The study was funded by Wellcome and the UKRI NIHR UK Coronavirus Immunology Consortium. The full study can be found at: https://www.nature.com/articles/s41590-025-02301-9 (URL will be live once the embargo lifts).
Source: Sanchez-Garcia, M. A., et al. (2025). Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity. Nature Immunology.doi.org/10.1038/s41590-025-02301-9
