Immune cells have a surprising and critical role in controlling movement and bridging neural activity with metabolic demands, concludes a groundbreaking study published in Nature by researchers at the University of Copenhagen and Imperial College London. This discovery opens exciting new avenues for treating motor disorders and metabolic conditions.
Your body is made up of approximately 30 trillion cells, each of them playing a unique role in keeping you alive and functioning. Among them, there are the immune cells known for defending against infections and aiding in wound healing. Until now.
A European collaboration between the University of Copenhagen and the Imperial College (UK) identified a particular type of immune cells, the macrophages, that play an unknown role in how you move.
"This study reveals, for the first time, that macrophages within muscle spindles actively participate in motor control through fast neurotransmitter-mediated mechanisms, typically associated only with neurons, challenging the classical view of macrophages as purely immune cells," says Carmelo Bellardita, associate professor and group leader at the Department of Neuroscience at the University of Copenhagen.
In addition to their well-known immune functions, macrophages in muscle spindles perform two newly identified roles: they modulate neural activity to control movement and couple the body's metabolic demands during movement to neural activity.
This means that macrophages help fine-tune muscle contractions, providing essential feedback to the nervous system and optimizing energy use during physical activity.
"Muscle spindles, where macrophages are located, are tiny sensors inside your muscles that help your body monitor how stretched or tense your muscles are. These sensors play a crucial role in guiding your movements," says Carmelo Bellardita.
For example, if you touch your nose with your eyes closed, muscle spindles detect the movements of the muscles in your arm and send signals to your brain. This feedback allows your brain to adjust and control the motion, ensuring your hand reaches your nose accurately—even without the help of your vision.
"This study adds new dimensions to how the brain integrates sensation and action by demonstrating that macrophages directly modulate their activity, coupling immune response to motor function while bridging energy demands with neural responses during movement," says Carmelo Bellardita.
New treatment possibilities
To find out the role of macrophages in controlling movement, the researchers combined different, advanced methods.
"We combined mouse intersectional genetics, optogenetic, and electrophysiological techniques to show how muscle spindle-resident macrophages activate sensory neurons via glutamate signaling, influencing neural activity, muscle contractions, and locomotion," says Carmelo Bellardita.
Glutamate signaling is a fast-acting communication system commonly associated with nerve cells, playing a critical role in essential brain functions such as memory, learning, and movement.
These macrophages use glutamate to modulate sensation and activate muscles. In turn, the contractions in the muscles produce glutamine, which reactivates the macrophages, creating a continuous feedback loop. This intricate mechanism highlights the macrophages' role as key integrators of immune, sensory, and metabolic functions in movement control.
"The multiple roles of macrophages in the neural, metabolic, and immune systems may have profound implications across diverse classes of pathologies," says Carmelo Bellardita.
In conditions like stroke, Parkinson's disease, and diabetes, where inflammation, energy deficits, and disrupted neural circuits exacerbate disease progression, targeting macrophage dysfunction could offer a novel therapeutic avenue. By harnessing their ability to modulate neural activity, fine-tune energy balance, and repair tissue, these immune cells may become key players in strategies to slow degeneration, restore motor function, and improve metabolic health.
"This groundbreaking work not only reshapes our understanding of movement control but also sets the stage for innovative treatments that address the interconnected nature of immune, neural, and metabolic dysfunctions," says Carmelo Bellardita.
