New findings link low oxygen to lasting changes in neutrophils
Hypoxia, or low blood oxygen, is not only a short-term stress on the body. New research shows it can reprogram a crucial immune cell—neutrophils—by altering the way their genetic material is packaged and read. This discovery helps explain why people who recover from severe lung conditions may remain vulnerable to infections for months.
How hypoxia affects neutrophils and their bone marrow origins
Neutrophils are among the body’s first responders to infection, rushing to sites of invading microbes to destroy them. The study, conducted by researchers at the University of Edinburgh, examined neutrophils from patients recovering from acute respiratory distress syndrome (ARDS) and from healthy volunteers exposed to high-altitude, low-oxygen environments. The scientists found that low oxygen levels change the way the cells’ DNA is packaged, which in turn alters gene activity and neutrophil behavior.
Crucially, the team observed that these changes were not limited to mature neutrophils. The same DNA packaging alterations appeared in bone marrow precursor cells—the cells that produce neutrophils. This suggests that hypoxia can imprint a “reprogrammed” state on the immune system at the source, influencing how new neutrophils respond long after oxygen levels return to normal.
What is histone clipping and why does it matter?
The researchers identified a process called histone clipping as a key mechanism behind these changes. Histones are proteins around which DNA is wound; clipping alters how tightly or loosely DNA is organized. When histones are clipped, chromatin structure shifts, changing which genes are accessible for activation or repression. This can lead to neutrophils that behave differently in the face of infection, potentially reducing their effectiveness in eradicating microbes.
Clinical implications: a lasting impact on infection defense
The findings provide a plausible explanation for a troubling clinical pattern: individuals recovering from severe respiratory illnesses, including ARDS, often experience recurrent infections or slower recoveries. If the immune system’s early responders are effectively reprogrammed by prior hypoxia, it could take time—or alternative strategies—to restore robust infection defense.
Dr. Manuel Alejandro Sanchez Garcia, a Postdoctoral Research Fellow at the Centre for Inflammation Research, emphasized the potential importance of recognizing these long-term changes. “Understanding that low oxygen levels have a lasting imprint on how early responder immune cells read their genetic code is essential,” he noted. “This could reshape how we treat people recovering from severe respiratory conditions.”
Future directions: reversing the imprint and boosting defenses
Edinburgh researchers are now planning studies to uncover what triggers these lasting changes, how persistent they are, and whether they can be reversed. If scientists can identify interventions that recalibrate histone clipping or the broader epigenetic marks left by hypoxia, they may open new avenues to strengthen infection defense in patients after serious lung diseases.
Why this matters for patient care
These discoveries highlight a need to monitor immune recovery more closely in patients who have endured hypoxic episodes, such as severe pneumonia, ARDS, or other conditions that impair oxygen delivery. Beyond immediate treatment, future therapies could be developed to restore the immune system’s readiness to fight infection, reducing the risk of repeated illnesses and improving long-term outcomes.
About the researchers
The study was conducted by scientists at the University of Edinburgh, with contributions from clinicians and researchers focused on inflammation and immune regulation. Their work underscores the complex relationship between oxygen availability, genetic regulation, and immune function.
