A new study published in Nature Medicine reported a surprising role of immune system in the aftermath of heart attacks. The findings revealed a new potential therapeutic opportunity to prevent heart attacks from progressing to heart failure in patients.
Ischemic heart disease is the most common cause of death in the world and it begins with a heart attack. During the process, heart cells die, prompting immune cells to enter the dead tissue, clear debris and orchestrate stabilization of the heart wall.
The researchers wanted to study the dying cells in the heart that stimulates the immune system. Hence they observed deep inside thousands of individual cardiac immune cells and mapped their individual transcriptomes using a method called single-cell RNA-Seq.
The study led to the discovery that after a heart attack, DNA from dying cells pretences as a virus and activates an antiviral program called the type I interferon response in specialized immune cells [interferon inducible cells (IFNICs)].
The team found that blocking the interferon response, either genetically or with a neutralizing antibody given after the heart attack, decreased inflammation, heart dysfunction, and improved survival from 60% to over 95%.
The study investigator King said, the researchers were interested to learn whether interferons contribute to adverse cardiovascular outcomes after heart attacks in humans. The immune system has evolved innate antiviral programs to defend against a diverse range of invading pathogens.
Immune cells do this by detecting molecular fingerprints of pathogens, activating a protein called IRF3, and secreting interferons that orchestrate a defence program mediated by hundreds of interferon-stimulated genes.
However, the team found that the antiviral interferon response is also turned on after a heart attack despite the absence of any infection. The results point to dying cell DNA as the cause of this confusion because the immune system interprets it as the molecular signature of a virus.
Surprisingly, the immune cells participating in the interferon response were a previously unrecognized subset of cardiac macrophages. These cells could not be identified by conventional flow sorting because unique markers on the cell surface were not known.
The researchers examined the expression of every gene in over 4,000 cardiac immune cells and found the specialized IFNIC population of responsible cells using single-cell RNA Seq (a technique that combines microfluidic nanoliter droplet reactors with single cell barcoding and next-generation sequencing).
The researchers aimed to further studies required to provide insights into the interferon response and the IFNIC cell type and explore their roles in the infarcted and remodelling heart. The team would also work to understand the interferon response in other tissues and diseases where cell death occurs.