Think of it as communicating with Silly String. When some of our white blood cells detect viruses or other microbes that have invaded our bodies, they may alert other cells to the threat by spraying out some of their DNA. This unexpected warning system, described in a study out this week, could hasten the body’s response to pathogens.
“It might be a new way for immune cells to detect infections and get rid of them,” says innate immunologist Paul Kubes of the University of Calgary in Canada, who isn’t connected to the study.
Researchers already know that some of our cells deploy DNA to directly fight infections. Immune cells known as neutrophils can eject their DNA, forming a mesh of sticky strands called a neutrophil extracellular trap (NET) that captures and kills microbes. Other immune cells generate similar DNA snares. The material for these traps often comes from the nucleus, but it can also spring from mitochondria, cells’ energy-producing power plants.
In the new study, a team led by biochemist Björn Ingelsson and immunochemist Anders Rosén of Linköping University in Sweden investigated whether NETs might also spur the growth of cancerous white blood cells in one type of leukemia—something scientists had previously hypothesized. While testing that idea, the researchers noticed something peculiar about cancerous cells that had been removed from leukemia patients and were growing in lab dishes.
The abnormal white blood cells—known as B cells—sometimes released skeins of DNA similar to NETs. These DNA webs, as the researchers call them, weren’t just a quirk of leukemia cells. The scientists demonstrated that B cells from healthy people also squirt out DNA in response to the distinctive molecular patterns that occur in many bacteria and viruses. Four other types of white blood cells also produce the webs, the team reported online this week in the Proceedings of the National Academy of Sciences. Sequencing the discharged DNA showed that it came from mitochondria, not the nucleus.
The mitochondrial DNA (mtDNA) webs unleashed by the white blood cells differ from NETs in several ways. For one thing, they lack the microbe-killing proteins that decorate NETs. And the cells that eject them survive—NET-spewing neutrophils often die after releasing their DNA. That may be because the webs come from mitochondria, which carry extra copies of their DNA. So cells may be able to spare some mtDNA, Rosén says.
But if the mtDNA webs don’t carry pathogen-slaying proteins, how can they protect us? The webs instead serve as signals between immune cells, the researchers’ findings suggest. The DNA triggers other white blood cells to release proteins known as type 1 interferons, which help our bodies fight viruses and some bacteria. But so far, researchers have not been able to pin down which receptor molecules allow immune cells to respond to the mtDNA alarm.
Although our bodies have several mechanisms for identifying threats and notifying other cells, “we have discovered a parallel signaling system for cell danger,” Rosén says. The advantage of mtDNA as a warning may be speed, says Ingelsson, who sees it as “a rapid messenger molecule” that can induce a protective response in minutes. Other immune defenses typically require hours or even days to mobilize.
The authors “have done a pretty good and exhaustive job of showing that these webs are different than anything we’ve encountered before,” Kubes says. But without further study in live animals, “it’s impossible to say” how important the webs are for fighting infection, cautions microbiologist Victor Nizet of the University of California, San Diego.
Rosén, Ingelsson, and colleagues are delving deeper into the webs’ roles in diseases and injuries. Other studies have found high levels of free-floating mtDNA in patients who have been wounded or suffer from a variety of illnesses, including heart disease, certain infections, and autoimmune diseases such as lupus. But whether this DNA is the same as the newly documented webs remains unclear.