Homing pigeons navigate with the help of macrophages in the liver

Homing pigeons (Columba livia domestica) can return to their loft from unfamiliar release sites. They do not rely on a single cue to do this. Sunlight, visual landmarks, environmental odors, and the geomagnetic field may all contribute to their navigation. When the sky is clear, the position of the sun can provide a stable directional reference. When the sky is completely overcast, however, solar and polarized-light cues disappear, and visual landmarks become less reliable. Under these conditions, pigeons may still maintain their course by relying on Earth's magnetic field. The unresolved question is where, in the body, birds detect magnetic information. This issue has been debated for decades. Three main ideas have been proposed: first, cryptochromes in the eye may form light-induced radical pairs, whose unpaired electron spins are affected by magnetic fields; second, iron-containing particles in the beak may align with the geomagnetic field and relay directional information through the trigeminal nerve; third, magnetic fields may influence cell membranes or ion channels and thereby alter neuronal activity. Each hypothesis explains part of the phenomenon, but none fully accounts for all aspects of avian magnetoreception.

A flock of homing pigeons in flight（Image source：Laitche， CC BY-SA 4.0 ）

A recent study therefore proposed a very different possibility: geomagnetic navigation in homing pigeons may depend on macrophages in the liver. Macrophages are phagocytic cells of the innate immune system. They reside in many tissues throughout the body, where they engulf and clear dead cells, cellular debris, and pathogens. The researchers first used vibrating sample magnetometry to examine different pigeon organs, including the liver, spleen, muscle, and the inner and outer beak. They found clear superparamagnetic signals in the liver and spleen at low temperatures, with the liver showing the stronger signal. Muscle and beak tissue showed much weaker magnetic responses. This suggested that the pigeon liver may contain iron-related structures capable of producing a magnetic response. The researchers then used Prussian blue staining to detect ferric iron. They found many iron-containing cells near the hepatic sinusoids, only a few in the spleen, and no comparable iron-positive cell distribution in the brain, muscle, eye, or beak.

Vibrating sample magnetometer（Image source：Jérôme， CC BY-SA 3.0 ）

Prussian blue staining of pigeon liver tissue; blue indicates macrophages（Courtesy of Lisowski C et al. (2026)）

The appearance and location of these iron-containing cells resembled macrophages. To test whether they were indeed macrophages, the researchers used clodronate liposomes, a preparation that is taken up by macrophages and induces macrophage depletion. It is commonly used to temporarily eliminate macrophages in vivo. Twenty-four hours after intravenous clodronate liposome injection, all relevant measurements of iron-containing cells in the pigeon liver showed a marked decrease. These findings indicated that the cells responsible for the superparamagnetic signal were most reasonably identified as iron-rich hepatic macrophages.

But if immune cells in the liver detect magnetic fields, how would that information reach the brain? Examination of pigeon liver tissue showed that iron-positive macrophages were located near hepatic nerve fibers. Histological staining revealed nerve bundles in the region of the hepatic portal triad, and iron-containing macrophages appeared in close proximity to these neural structures. Electron microscopy further revealed bundles of unmyelinated axons, neurofilaments, neurotransmitter vesicles, and other features of nerve fibers, with macrophages often located nearby. These findings do not directly prove that signals pass from macrophages to nerves, but they do provide a plausible anatomical basis: hepatic macrophages may communicate magnetic information to the brain through close interactions with the autonomic nervous system.

Hepatic portal triad outlined by the dashed circle（Image source：Zorn, A.M.， CC BY 3.0 ）

Electron microscopy image showing a macrophage in blue and nerve fibers in yellow（Courtesy of Lisowski C et al. (2026) ）

The strongest evidence came from behavioral experiments. The researchers trained 34 pigeons to return home from a release site about 19 kilometers to the west. After 10 successful training flights, the birds were assigned to either a control group or a clodronate liposome–treated group when the weather forecast predicted completely overcast conditions for the next day. Twenty-four to 28 hours later, the pigeons were released individually under fully overcast skies and tracked with real-time GPS devices. The result was striking. All control-treated pigeons returned home within 70 minutes. By contrast, none of the clodronate-treated pigeons returned on the same day under persistent overcast conditions, and their flight directions became scattered. Yet when the clouds cleared and the sun became visible, these treated pigeons were again able to return home normally. The researchers also later treated the original control pigeons with clodronate liposomes and tested them under sunny conditions; they still homed efficiently. This indicates that pigeons rely on different navigational cues under sunny and overcast conditions.

The study proposes the following interpretation. Hepatic macrophages may gradually accumulate ferric iron because they participate in the clearance of aged or damaged erythrocytes and in iron metabolism. This iron is stored in forms such as ferritin, giving the cells collective superparamagnetic properties. The magnetic signal from a single cell may be very weak, but if many macrophages act as a population-level sensing system, their combined response may be sufficient to influence nearby nerve endings. Such signals could be transmitted through mechanical coupling, changes in intracellular organization, paracrine release of soluble mediators, or other macrophage–nerve communication pathways. The brain could then integrate this magnetic input with other sensory cues to generate a directional sense useful for flight.

Although the exact mechanism of macrophage–nerve communication remains unresolved, this study shows that when the sun is hidden behind clouds, one of the key cues guiding pigeons home may lie deep inside the liver, in a population of iron-bearing macrophages.

Author: Shui-Ye You

Reference:

Lisowski C et al. (2026). Homing pigeon navigation relies on superparamagnetic macrophages under overcast conditions. Science.