The immune system sits at a delicate balance, without a properly functioning immune system we are susceptible to disease, cancer and other ailments, but an overactive one can be almost as devastating to our health. This balance comes to play following a heart attack—immune cells clear dead heart cells and orchestrate stabilization of the heart wall, but this can lead to excess inflammation and inhibit cardiac function.
While the cause of this immune activation was previously unknown, a team of scientists from the University of California San Diego and other institutes report finding a surprising role for the immune system following heart attacks. Their findings were published yesterday in Nature Communications.
For this study, the researchers mapped the individual transcriptomes of thousands of individual cardiac immune cells using single cell RNA-Seq. They discovered that DNA from dying cells masquerades as a virus, activating type I interferon response in specialized immune cells. The researchers named these cells interferon inducible cells (IFNICs). Blocking interferon response in mice following a heart attack revealed less inflammation, less heart dysfunction, and improved survival. Blocking antiviral response increased survival from 60 to over 95 percent.
The immune cells participating in the interferon response were a previously unrecognized subset of cardiac macrophages that were never identified through cell sorting since their surface markers were unknown. RNA-Seq allowed the researchers to examine gene expression in 4,000 cardiac immune cells to pinpoint the precise population.
These findings could someday lead to new treatments for heart disease.
Using single cell RNA-Seq, a technique that combines microfluidic nanoliter droplet reactors with single cell barcoding and next generation sequencing, the researchers were able to examine expression of every gene in over 4,000 cardiac immune cells and found the specialized IFNIC population of responsible cells. Image courtesy of the University of California San Diego