‘Mind-blowing’: Iron-rich immune cells help homing pigeons navigate

Of all the myriad animal senses, the most mysterious and controversial is the perception of magnetism. Somehow, migratory songbirds, sea turtles, and other creatures detect Earth’s magnetic field and use its directionality to help them navigate. Now, a paper published in Science has found a surprising mechanism: Iron-rich immune cells within homing pigeons’ livers seem to give the birds their magnetic compass. “The concept … is just mind-blowing,” says Catherine Lohmann, a sensory ecologist at the University of North Carolina at Chapel Hill who was not involved. “It’s truly a new direction and a very fresh take on a controversy that’s been in the literature for a long time.” Many animals have magnetically informed senses of direction, including birds, turtles, sharks, and dogs. A few researchers even think humans might have a vestigial magnetic sense. Exactly how this sense works has been hotly debated. An early hypothesis was that minute crystals of magnetite embedded within the animals’ tissues somehow act like compass needles. A more recent idea is that proteins in the retina, called cryptochromes, react to magnetic fields; this would allow migrating songbirds to fly in the right direction even in the dim glow of twilight. Last year, researchers studying homing pigeons discovered another mechanism. Laboratory experiments revealed that varying magnetic fields induces electric currents in their inner ears, stimulating nerves that lead to the brain. The new study’s discovery in pigeons began with a serendipitous meeting. While attending a scientific conference, ornithologist Martin Wikelski, who studies migratory species at the Max Planck Institute of Animal Behavior, struck up a conversation with immunologist Christian Kurts of the University of Bonn. After Wikelski described the role of magnetism in animal navigation, Kurts mentioned he had found that immune cells called macrophages recovered from the spleens of mice and humans contained tiny magnetic iron particles that formed when the macrophages broke down old red blood cells and sequestered their iron atoms. Could similar immune cells be playing a role in homing pigeon navigation? Liver tissue with macrophages stained blue to reveal their magnetic ironLisowski et al.

Kurts had an idea how to test the hypothesis, so he brought in Bonn postdoctoral researcher Clivia Lisowski—who had long been fascinated by how cells sense their environment—to lead the investigation. “I was hooked,” she recalls. First, Lisowski checked whether various pigeon tissues displayed the same tiny magnetic particles as mice immune cells. She and her colleagues expected to find a hot spot in the spleen, which in mammals is the primary location where macrophages recycle red blood cells. Instead, a sensitive magnetometer showed the liver had the strongest signal of all the tissues tested. It was relatively faint but still more than 20 times the instrument’s background noise level. Careful staining of thin slices of homing pigeon tissue confirmed that a form of iron called ferritin abounded in liver macrophages but was scarce in the spleen and absent in the beak or brain. A closer look with an electron microscope also showed many of the pigeons’ liver macrophages were right next to neurons. In mammals, neurons in the spleen can communicate with macrophages, and in both mammals and birds, these neurons also connect to the central nervous system. Next, the researchers tested whether these iron-rich macrophages act as magnetic compasses for the pigeons through a simple, elegant experiment: knocking out the macrophages with a drug called clodronate liposomes. The team trained 34 homing pigeons, a variety bred for their skilled wayfinding, to fly a 19-kilometer route due east. During the day, pigeons use the position of the Sun to orient themselves. But when it’s cloudy and completely overcast, they rely on their magnetic sense to get their bearings. Near Lake Constance, the team injected 18 birds with clodronate and, 24 hours later, released them one by one when dense clouds completely blocked the Sun. The birds were outfitted with GPS transmitters, so the team could track the birds in real time. Homing pigeons orient themselves by the Sun’s position under sunny skies and rely on their magnetic sense when it is cloudy. Under overcast conditions, homing pigeons with their normal liver macrophages had little issue flying a 19-kilometer route for which they had been trained.

When injected with clodronate liposomes that knocked out the liver macrophages, the pigeons could navigate the route without issue when it was sunny. Under overcast skies, however, homing pigeons with depleted liver macrophages struggled mightily to find their way home—suggesting the immune cells play a role in the birds’ magnetic sense. Max Planck Institute of Animal Behavior All 18 birds got hopelessly lost, only returning home after the skies had cleared. In contrast, 16 birds released after getting sham injections immediately flew straight home. “For me that was the first indication that there’s something really exciting going on,” Wikelski says. To rule out the possibility that the drug had disoriented the birds or caused other side effects to make them lose their way, the researchers released drugged birds on sunny days. They flew home just fine. “This is an extraordinarily exciting finding,” says Verner Bingman, a neuroethologist at Bowling Green State University. Still, he views the study as “a proof of concept” that should be investigated further. Rather than knocking out the macrophages, Bingman would like to see an experiment in which magnetic information from the liver is manipulated. Similar interventions were made during experiments in the 1970s, when researchers outfitted homing pigeons with metal coils that altered the magnetic fields around their heads, causing them to fly in the opposite direction. Susanne Åkesson, an animal ecologist at Lund University, says several questions remain about the potential role of the liver in navigation, such as how the macrophages might be passing magnetic information to nearby neurons. One idea is that as the bird shifts its position relative to Earth’s magnetic field lines, the ferritin changes orientation and tugs on the web of fibers within a macrophage, possibly triggering the release of signaling molecules. If the ferritin mechanism is confirmed, Wikelski says, it “could be very general from bees to bats to whales to sharks.” But Lohmann remains cautious. Unlike a homing pigeon flying home, the study of animals’ magnetic sense has rarely taken the straight, narrow path. “I think time will tell whether it’s correct or not,” Lohmann says, “but it’s intriguing.”