Researchers have discovered a DNA shift in the innate immune memory of cells. This finding may aid in the fight against sepsis. The medical condition is not only potentially life-threatening it also places a considerable financial burden upon health systems.
The scientists demonstrated that changes to the structure and organization of DNA create an exhausted memory state in monocytes, the white blood cells that facilitate immune responses in the body. This is a marker for the novel phenomenon of innate immune memory.
In the body’s innate immune system, monocytes migrate through the bloodstream to sites of tissue damage or infection and orchestrating the initial immune response.
The findings stem from previous inquiries into white blood cells’ role in immune dysregulation during sepsis.
It appears that therapeutic interventions can prevent the DNA change and help the white cells stay in better fighting shape to help combat bacterial infections. This could be achieved through a drug that blocks the acquisition of DNA methylation. Through this, the researchers hope to be able to change the behaviour of the monocytes and hence to restore normal monocyte activity.
According to Blake Caldwell, a Virginia Tech Presidential Postdoctoral Fellow: “We found there’s a critical involvement of DNA methylation in controlling innate immune memory.”
Caldwell adds: “DNA methylation is when a small molecule called a methyl group gets added to DNA, proteins or other molecules. This impacts the capacity of monocytes to remember a past immune challenge and change their behaviour in the future.”
DNA methylation is one of the main epigenetic modifications. It controls gene expression through altering chromosomal structure.
This exhausted state contributes to most sepsis patients’ immune systems remaining critically disabled for months or years after the initial shock is treated.
Caldwell’s team discovered that DNA methylation plays a large role in the long-term misbehaviour of the white blood cells in sepsis and other severe immune conditions. And by blocking this change from occurring, researchers can right the behaviour of the cells, which has implications beyond sepsis alone.
Going forwards it is possible that the findings around sepsis could provide a wider medical model for the innate immune system that could be applied more broadly given that the the same pathways are activated by COVID-19, coronary artery disease, and other severe immune events.
The research has been published in the journal Cell Reports. The study is titled “Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis.”
