Heat as a turbo-boost for immune cells

Temperature is a key physiological factor that determines the speed of immune reactions. While this may seem obvious, it has remained largely unexplored at the single-cell level—until now. Stefan Wieser from the Institute of Zoology at the University of Innsbruck and his colleagues report in Developmental Cell that the motor protein Myosin II regulates the temperature sensitivity of immune cells and drives the acceleration of immune responses at elevated body temperature.

Wieser first noticed that temperature affects the movement of immune cells inside the body about ten years ago, through simple cell-culture experiments conducted at the Institute of Science and Technology Austria (ISTA). He observed that gradually increasing the incubator temperature from 20 °C to 40 °C dramatically altered immune-cell motility: the warmer the environment, the faster the cells moved—while at 20 °C they almost completely stopped. But uncovering the molecular mechanism behind this phenomenon took many more years.

“It sounds surprising, because the idea that immune cells react to temperature seems obvious,” explains the biophysicist, “yet there was no clue as to how this mechanism could work at the molecular level.” Together with co-author Verena Ruprecht, Wieser now investigates such questions in the newly established Quantitative Biology (QBIO) group at the Institute of Zoology.

The topic never left him. During his time as a group leader at the Institute of Photonic Sciences (ICFO) in Barcelona, Wieser had the opportunity to study temperature sensitivity in immune cells systematically—both in cell cultures and in living organisms such as zebrafish and mice—using a custom-built thermo-microscope. The team’s results are presented in the current issue of Developmental Cell.

Myosin II in Feverish Motion

When the temperature increased from 25 °C (“cold”) to 37 °C (“normal”) and 41 °C (“fever”), several types of human leukocytes—including T cells, macrophages, dendritic cells, and neutrophils—showed a marked rise in migration speed and a significantly higher number of cells entering lymphatic vessels within a short time.

“By ‘significant’ we mean up to a tenfold increase in speed, which can drastically shorten the time it takes immune cells to reach lymphatic vessels,” Wieser explains. Moreover, leukocytes responded almost instantaneously—within seconds—to temperature changes. “This clearly pointed to a biophysical mechanism, faster than any gene-regulation process,” he adds.

Using a sophisticated fluorescence-microscopy setup that allows precise temperature control at the single-cell level, Wieser and his colleagues were able to pinpoint the underlying mechanism: the motor protein Myosin II. Known for its roles in cell motility, cell division, and muscle contraction, Myosin II increases its ability to generate mechanical force via ATP when temperatures rise above 37 °C—thus propelling immune cells more rapidly. Myosin II is therefore the key driver of an efficient immune response under fever-like conditions.

“Our study shows that temperature is a crucial physiological control parameter that autonomously modulates both speed and morphological dynamics at the single-cell level in warm- and cold-blooded species alike,” Wieser concludes. He sees the findings as a starting point for new research questions—particularly in physiology and immunology.