Daylight boosts the immune system's ability to fight infections

Our bodies are finely tuned to time. From sleep patterns to hormone levels, internal clocks influenced by light regulate every cell. Now, scientists at Waipapa Taumata Rau, University of Auckland, have found that our immune system also tells time and works better during the daylight hours.

The study reveals that neutrophils – our most common white blood cells – have their own internal clock. This clock listens to daylight and responds by boosting immune strength. The work builds on previous findings but goes further to decode the genetic machinery linking light to immunity.

The implications are wide. From shift workers to those with chronic inflammation, this research could change how and when we treat infections.

The discovery was led by Professor Christopher Hall, along with researchers from the University of Auckland. The findings add new depth to the fast-growing field of chronobiology.

Discovering the immune clock

To explore how light affects immunity, the scientists turned to zebrafish. These small freshwater fish share a surprising amount of genetic similarity with humans.

More importantly, their transparent bodies allow researchers to observe immune cells live, under a microscope, without needing surgery or dyes.

“In earlier studies, we had observed that immune responses peaked in the morning, during the fish’s early active phase,” said Hall. “We think this represents an evolutionary response such that during daylight hours the host is more active so more likely to encounter bacterial infections.”

Zebrafish became the perfect test subjects. Infections were introduced, light conditions were altered, and the activity of neutrophils – the first responders of our immune system – was tracked minute by minute.

The results clearly showed that these cells were more aggressive and efficient during the day.

Immune cells have clocks

As it turns out, neutrophils do not simply respond passively to external cues. They contain their own circadian clock, driven by a core gene called per2. This gene senses daylight and activates a bacterial killing program inside the cell.

When the scientists removed or deactivated per2 in zebrafish, the immune response weakened. Even during the day, neutrophils in these mutants failed to control infections as effectively. Bacterial survival rates increased, and inflammation worsened.

Further investigation showed that when light was restored, per2 became active again. Its presence resulted in better bacterial clearance and stronger neutrophil behavior.

The day-night cycle, therefore, was not just setting the rhythm of sleep or alertness, but directly influencing immune strength at the cellular level.

Daylight genes help immune cells

But per2 was only part of the picture. The real killing power of neutrophils comes from reactive oxygen species (ROS). These toxic molecules are used to break down invading bacteria. And the production of ROS relies on another gene: hmgb1a.

The researchers discovered that when per2 is active, it triggers higher expression of hmgb1a. This leads to greater ROS production and improved bacterial killing. When either gene is disrupted, neutrophils lose this power.

In fact, overexpressing per2 or hmgb1a rescued the immune response even in fish kept in constant darkness.

This showed that the pathway could be activated genetically, independent of light, and offered possible targets for future drug development. The system was robust, precise, and deeply tied to environmental light cycles.

Daylight helps immune cells fight

While per2 acted as the accelerator, another protein, Cry1a, functioned as a brake. Cry1a is known to repress the activity of the circadian clock. In the immune system, this repression turns into a reduction in neutrophil efficiency.

Mice and zebrafish with inactive Cry1a fought off infections more effectively. The absence of Cry1a allowed per2 and hmgb1a to remain active longer, maintaining high ROS levels. This discovery led to a deeper understanding of how balance is maintained in immune timing.

To test these findings further, the team created zebrafish mutants that lacked both per2 and Cry1a. The double mutants behaved like the Cry1a-only mutants. In other words, per2 normally works by blocking Cry1a’s suppression of immune activity.

The results show that, in this battle of clock proteins, light tips the scale in favor of the immune system.

Presence of light-activated proteins

The final layer of this mechanism lies in gene regulation. Neutrophils use a DNA region called CNS4 to turn on hmgb1a. This region includes docking points for two important proteins: BMAL1 and NF-κB. These proteins act like keys, unlocking hmgb1a only when the timing is right.

In the presence of light, BMAL1 binds strongly to CNS4. This primes the cell for infection response, making it more effective at producing ROS. If the CNS4 region is deleted or BMAL1 is blocked, neutrophils lose this ability. Their response weakens, and hmgb1a levels fall.

This region of DNA is highly conserved across vertebrates – from fish to birds to mammals. That suggests this light-controlled immune pathway is not just a zebrafish feature.

It is a shared biological strategy, built through millions of years of evolution, to fight bacteria more effectively during times of activity.

Implications for human health

“Given that neutrophils are the first immune cells to be recruited to sites of inflammation, our discovery has very broad implications for therapeutic benefit in many inflammatory diseases,” said Hall.

This knowledge might change how we treat infections. For example, drugs that target the circadian machinery of neutrophils could help those with compromised immune systems. Such treatments could be timed with daylight exposure to maximize their effect.

People working night shifts or suffering from jet lag might also benefit. Their disrupted light cycles could be weakening immune responses. Light-based therapies, or drugs that mimic per2 activation, might restore balance.

Improving how we fight infections

“This finding paves the way for development of drugs that target the circadian clock in neutrophils to boost their ability to fight infections,” noted Hall.

The research was supported by the Royal Society of New Zealand’s Marsden Fund. Though done in zebrafish, the genetic pathways discovered – per2, Cry1a, hmgb1a, and CNS4 – are present in humans too.

Ongoing work now aims to unravel how light fine-tunes these molecular switches in more detail. By understanding the clockwork inside each neutrophil, scientists are moving closer to tailoring immunity by the hour.

In the future, fighting infections might be as simple as switching on the lights – at just the right time.

The study is published in the journal Science Immunology.

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