The immune system and the body's internal clock are intimately tied.

Blood cells that fight disease ebb and flow with the body's daily circadian rhythms. Levels of circulating T-cells peak at nighttime, for example, and then gradually subside. Studies have also shown that the immune system reacts to certain infections by manipulating circadian clock genes, promoting sleep and causing the fatigue that often accompanies illness.

Now, new research helps solidify the idea that our susceptibility to infection depends on the time of day. A study at Yale University showed that even the success of vaccination may hinge on circadian fluctuations. The study, published in the journal Immunity, looked at mice, but its findings dovetail with previous research on humans and other animals.

The researchers found that circadian rhythms influenced levels of an immune protein called Toll-like receptor 9, or TLR9, causing a daily peak and nadir. When mice were exposed to bacteria at different times of day, those who were infected at the low point of TLR9 activity developed severe sepsis and died much sooner than those exposed when TLR9 was high.

In another phase of the study, mice vaccinated near the daily TLR9 peak had stronger immune responses than those vaccinated at the circadian low point.

The researchers pointed out that these fluctuations may have evolved as a way to maximize protection against diseases like malaria - carried by mosquitoes that typically exhibit daily feeding patterns. The research might also explain why jet lag, which throws off circadian rhythms, has been shown to affect immunity.


Immunity to infection, research suggests, varies with daily circadian rhythms.
