Temperature profoundly influences the immune system’s ability to respond swiftly and effectively, yet the molecular machinery behind this phenomenon has eluded researchers for years. A groundbreaking study led by Stefan Wieser and his team at the University of Innsbruck’s Institute of Zoology uncovers how immune cells harness the motor protein Myosin II to accelerate their movement under elevated temperature conditions, such as during fever, thereby enhancing immune responsiveness. Published in the prestigious journal Developmental Cell, this research illuminates the biophysical underpinnings of temperature-controlled immune dynamics, marking a paradigm shift in our understanding of cellular immunology at the single-cell level.
Immune cells are pivotal sentinels, constantly patrolling the body to detect and eliminate pathogens. Their ability to navigate tissues efficiently is crucial for timely immune responses. Intriguingly, this motility appears exquisitely sensitive to temperature changes, a fact that has been observed but not thoroughly dissected at the molecular scale. About a decade ago, Wieser’s initial experiments—conducted in cell culture environments—revealed that raising the ambient temperature from room temperature (20 °C) to near fever-level warmth (40 °C) resulted in a dramatic increase in immune cell motility. Cells cultured at lower temperatures exhibited markedly diminished movement, almost halting altogether, whereas warmer conditions propelled them into rapid motion. This observation hinted at a fundamental thermoregulatory mechanism waiting to be unraveled.
The enigmatic question was: what molecular processes enable immune cells to translate temperature shifts into altered behavior so promptly? Genetic regulatory pathways, typically requiring minutes to hours, could not explain the near-instantaneous acceleration observed. This discrepancy suggested that biophysical forces and rapid protein activity adjustments underlie the thermal responsiveness. Wieser, together with co-author Verena Ruprecht and their colleagues within the newly formed Quantitative Biology (QBIO) group, embraced an interdisciplinary approach combining cellular biology, biophysics, and high-resolution microscopy to probe these mechanisms with unprecedented precision.
A transformative phase of the research unfolded during Wieser’s tenure at the Institute of Photonic Sciences (ICFO) in Barcelona, where access to advanced imaging technologies enabled systematic examination of immune cell motility in both cultured cells and living models, including zebrafish and mice. Central to this investigation was the deployment of a custom-engineered thermo-microscope, designed to permit exact temperature manipulation at the single-cell level while simultaneously capturing dynamic cellular responses through fluorescence imaging. This innovative platform allowed the team to mimic physiological temperature gradients and observe immune cells’ mechanical adaptation in real time.
Their results were nothing short of remarkable. Among diverse human leukocyte populations—T cells, macrophages, dendritic cells, and neutrophils—the increase from 25 °C (commonly referred to as “cold”) through a physiological baseline of 37 °C, up to febrile temperatures of 41 °C elicited an exponential rise in migration velocity. Quantitatively, some cells exhibited up to a tenfold enhancement in speed. This rapid kinetic shift also translated to a greater number of immune cells infiltrating lymphatic vessels, a key step in mounting effective adaptive immune responses. The speed and immediacy of these changes effectively ruled out classical gene expression changes, pointing instead to an immediate molecular motor-based mechanism.
Enter Myosin II, a versatile motor protein well characterized for its roles in cellular contractility, locomotion, and cytokinesis. The team showed that Myosin II’s capacity to generate mechanical force is directly modulated by temperature oscillations, particularly when temperatures rise above the physiological norm of 37 °C. This temperature-dependent modulation hinges on Myosin II’s ATPase activity—its ability to convert chemical energy from ATP hydrolysis into mechanical work intensifies as thermal energy increases. This enhanced force production effectively propels immune cells faster through tissue matrices and facilitates quicker transendothelial migration.
Critically, this study highlights Myosin II’s function not merely in baseline cell motility but as a cellular thermostat that tunes immune responsiveness according to thermal cues. This thermosensitivity has profound physiological implications: fever, often perceived solely as a symptom, emerges here as an evolutionarily conserved mechanism that accelerates immune surveillance and response, providing a tangible molecular basis for the protective role of elevated body temperature during infection.
Beyond human cells, the researchers found indications that this thermo-adaptive mechanism is conserved across warm- and cold-blooded species alike, underscoring the fundamental nature of this regulatory pathway. This cross-species conservation opens intriguing avenues for broader ecological and evolutionary studies on immune system adaptability under varying environmental temperatures.
Technically, the research leveraged state-of-the-art fluorescence microscopy and quantitative biophysics to dissect the interplay between intracellular force generation and motility. The high temporal resolution of the thermo-microscope unveiled that leukocyte mechanical dynamics respond almost instantaneously—within seconds—to temperature shifts. Such immediacy delineates Myosin II-driven motility as a unique rapid-response mechanism distinct from slower biochemical signaling cascades or transcriptional regulation, underscoring the elegant efficiency of cellular mechanotransduction.
This newly elucidated role of Myosin II in temperature-dependent immune cell motility not only deepens our comprehension of immune physiology but also prompts a reevaluation of fever’s clinical significance. It suggests that therapeutic strategies manipulating Myosin II activity or mimicking thermal modulation might augment immune efficacy, particularly in immunocompromised or elderly patients whose febrile responses may be blunted.
Looking forward, Wieser and his colleagues anticipate that their findings will stimulate a wealth of novel research paths. Key questions include deciphering how Myosin II’s mechanical properties are biochemically tuned at different temperatures, how this motor protein integrates with other cytoskeletal components to modulate cell morphology and signaling, and whether similar thermo-adaptive mechanisms operate in other immune cell functions such as phagocytosis or cytokine secretion.
In sum, this pioneering work casts new light on the intricate relationship between temperature and immunity, establishing Myosin II as a central molecular player in the thermo-adaptability of immune responses. By bridging cellular biophysics with immunology, Wieser’s study paves the way for innovative explorations into how the body harnesses physical forces to safeguard health, particularly under the dynamic thermal conditions encountered during infection and inflammation.
Subject of Research: Cells
Article Title: Myosin II regulates cellular thermo-adaptability and the efficiency of immune responses
News Publication Date: 4-Nov-2025
Web References: DOI: 10.1016/j.devcel.2025.10.006
Image Credits: Stefan Wieser
Keywords: Immune cell motility, Myosin II, temperature sensitivity, febrile response, cellular biophysics, thermo-adaptability, immune response acceleration, fluorescence microscopy, ATPase activity, leukocyte migration
