Low oxygen Levels Can permanently Weaken Immune Response, Study Finds
New research from the University ofโ edinburgh reveals that low โbloodโข oxygen levels (hypoxia) can induce lasting changes to the โคgenetic makeup of neutrophils โข- key immune cells responsible for fighting โฃinfection – โultimately weakeningโ the โคbody’s defense mechanisms. The study, published in Nature Immunology, demonstrates that these changes can persist even โ after โคoxygen levels are restored.
Scientists discovered that hypoxiaโ altersโ how โDNA is packaged within neutrophils, impacting their ability โto effectively destroy harmful โขmicrobes. Critically,theโค research shows โthe impactโฃ isn’t limited to existing neutrophils; low oxygenโ also appears to leave a lasting mark on theโค bone marrowโ cells that produce โthese cells. This suggests a prolongedโข vulnerabilityโค to infection following periods of oxygen deprivation.
researchers studied neutrophilsโ from two โคgroups: patients recovering โขfrom acute respiratory distress syndrome (ARDS) and healthy volunteers exposed to theโข low-oxygen environments of high altitude.โฃ They found that in both groups,โข low oxygen triggered โa โฃprocess called “histone clipping” – a modification to proteins that organizeโค DNAโ – which altered gene expression. This change in how genes are switched โคon or off ultimately affected neutrophil behavior.
“Recognizing that low oxygen levelsโ have aโข long-lasting effect onโค how early responder immune cells read โtheir genetic code โขis โขimportant because it explains why these cells are less good at controlling infectionโ many months after a severe respiratoryโข illness,”โค explains Manuel Alejandro Sanchez Garcia, Postdoctoral Research Fellow at theโ University of Edinburgh’s Center for Inflammation Research. “The discovering opens upโค new ways toโ thinkโข about treating long-term immune dysfunctionโ and improve infection defenses.”
The โfindings โmay explainโ the increased susceptibility to repeated infections observed in individuals recovering from conditions likeโฃ severe โฃlung disease. The research team now plans to investigate the triggers behind โขthese โขlong-termโฃ changes and explore โpotential methodsโ to reverse them, โbolstering the body’s immuneโค defenses.
The study was funded by โขWellcome and the UKRI NIHR UK Coronavirusโ Immunology โคConsortium. The full studyโ canโ be foundโข at: https://www.nature.com/articles/s41590-025-02301-9 (URL โคwill be live once the embargo lifts).
Source: Sanchez-Garcia, M. A., et โal. (2025). โฃHypoxia induces histone clipping and H3K4me3 loss inโ neutrophil โขprogenitors resulting in long-term impairment of neutrophil immunity. โฃ Nature Immunology.doi.org/10.1038/s41590-025-02301-9
