To Sleep Is to Heal: How the Immune System Regulates Sleep When Sickness Strikes

On average, a human spends 25 years of their lifetime sleeping. That’s eight hours per day, 56 hours per week, and 2,912 hours per year. Whilst we rest and recharge for the morning ahead, the body and brain are extraordinarily active, embarking on a series of biological processes that restore and rejuvenate. When illness strikes, a visit to the doctors typically results in a prescription for plenty of sleep and rest. Inadequate sleep is known to be hazardous to good health, and can produce symptoms such as high blood pressure, obesity, diabetes and poor mental health.

A healthy sleeping pattern is integral for our survival. Yet, whilst we know the value of sleep and invest such a large proportion of our lives doing it, what remains elusive is the precise reasons as to why we do it.

The wonder and curiosity surrounding sleep has enthused decades of scientific research, and whilst significant progress has been made in our broader understanding of why we sleep, little has been made clear about the genetic or molecular forces driving the need to sleep, until now.

In a study utilising a fruit fly model, researchers from the Perelman School of Medicine at the University of Pennsylvania have identified a single gene, named NEMURI, that increases the need for sleep. Published today in Science, the research shows how the NEMURI protein, an antimicrobial peptide (AMP) fights germs with its inherent antimicrobial activity, and is secreted by cells in the brain to drive prolonged, deep sleep after an infection.

By knocking out the NEMURI gene so that it was no longer expressed, the scientists were able to study how the gene controls the flies’ sleep patterns. They found that the flies were more easily aroused during daily sleep, and that their acute need for an increase in sleep (induced by sleep deprivation or infection) was reduced.

"While it's a common notion that sleep and healing are tightly related, our study directly links sleep to the immune system and provides a potential explanation for how sleep increases during sickness," said senior author Amita Sehgal, PhD, a professor of Neuroscience and director of Penn's Chronobiology Program.

Interestingly, sleep deprivation, which naturally increases the need for sleep, stimulated NEMURI expression in a small set of neurons in the sleep-promoting structure of the brain. When inducing overexpression of NEMURI, increased sleep and survival in bacteria-infected flies was observed when compared to healthy control flies. As increased sleep during sickness promotes survival in the fly model, it is possible that the sleep-promoting role of the NEMURI protein is equally as important as it’s antimicrobial function.

“The findings suggest that sleep following prolonged wakefulness (sleep deprivation) relies upon similar pathways as sleep during sickness, supporting the idea that sleep deprivation is a stress/sickness,” adds Sehgal.

How does this research pave the way for further exploration into the link between immune system and sleep? Sehgal comments “As far as we know, humans do not have the molecule we report here, NEMURI.  However, they have similar kinds of molecules—anti-microbial peptides (AMPs).  Future research could examine whether AMPs affects sleep in mammalian models e.g. mice, which may be indicative of similar functions in humans.”

References:

Toda et al. 2019. A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science. http://science.sciencemag.org/cgi/doi/10.1126/science.aat1650. 

Goran Medic, Micheline Wille, and Michiel EH Hemels. 2017. Short- and long-term health consequences of sleep disruption. doi: 10.2147/NSS.S134864.