The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity

[Anne]

free full text
http://download.cell.com/immunity/pdf/PIIS1074761312000477.pdf?intermediate=true


Immunity, 16 February 2012
Copyright ? 2012 Elsevier Inc. All rights reserved.
10.1016/j.immuni.2011.12.017

Authors

Adam C. Silver, Alvaro Arjona, Wendy E. Walker, Erol Fikrig

See Affiliations

• Highlights
• The circadian molecular clock modulates Tlr9 expression and function
• There are in vivo daily variations in the responsiveness to CpG ODNs (TLR9 ligand)
• The time of day determines disease severity in a TLR9-dependent sepsis model
• Timing of immunization determines TLR9 ligand-adjuvanted vaccine responsiveness

Summary

Circadian rhythms refer to biologic processes that oscillate with a period of ∼24 hr. These rhythms are sustained by a molecular clock and provide a temporal matrix that ensures the coordination of homeostatic processes with the periodicity of environmental challenges. We demonstrate the circadian molecular clock controls the expression and function of Toll-like receptor 9 (TLR9).
In a vaccination model using TLR9 ligand as adjuvant, mice immunized at the time of enhanced TLR9 responsiveness presented weeks later with an improved adaptive immune response.
In a TLR9-dependent mouse model of sepsis, we found that disease severity was dependent on the timing of sepsis induction, coinciding with the daily changes in TLR9 expression and function. These findings unveil a direct molecular link between the circadian and innate immune systems with important implications for immunoprophylaxis and immunotherapy.

 

[Tonka]

Re: The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity

http://www.elmostrador.cl/vida-en-l...-biologico-altera-la-inmunidad-a-infecciones/
Spanish-English translation

Our biological clock alters immunity to infection

The time of day seems to have a significant impact on our risk of acquiring an infection, reveals research in the United States.
by BBCCOMMENTSEND RECTIFY PRINT

The time of day seems to be an important factor in our risk of acquiring an infection, a study in the United States.

Researchers at the Medical School of Yale University discovered how a protein of the immune system is affected by chemical changes that occur in our body throughout the day.

The finding, published in the journal Immunity , shows that an infection is less or more severe depending on the time of day.

These results, experts say, can have an impact on the future in how drugs are given.

Plants, animals and even bacteria undergo a routine that changes every 24 hours, the so-called circadian rhythm.

When the body is out of adjustment in the pace of their environment, for example when crossing time zones when traveling long haul, occurs the so-called jet lag .

It is known that the immune system has variations throughout the day. Although the new research now seems to have found how these variations occur and what are its effects.

PATHOGEN DETECTION
For the immune system to fight infection needs to first detect the invading pathogen.

The Yale researchers were analyzing one of the proteins involved in this process of detection, Toll-like receptor 9 (TLR9).

This receiver can identify DNA of bacteria and viruses.

In experiments with mice, scientists found that the amount of TLR9 produced and how it works are controlled by the body's biological clock and this process varies throughout the day.

They found that when mice immunized at the time of maximum activity of TLR9, improved immune system response.

According to the researchers, it is known that humans who develop sepsis, a lethal infection in the blood tend to be at increased risk of death between 02:00 and 06:00 am.

In the experiment with mice, the severity of sepsis was dependent on time of day when the infection began, and this coincided with changes in the activity of TLR9.

As explained by Professor Erol Fikrig, who led the research, they found "a direct molecular link between circadian rhythms and the immune system."

And this, adds, "could have important implications for prevention and treatment of diseases."

"It seems that disturbances in the circadian clock influence our susceptibility to pathogens" says the scientist.

For his part, Dr. Akhilesh Reddy, who is investigating the University of Cambridge in circadian rhythms, notes that it has long been known that the time has an impact on the immune system, but this study is one of the first forays into the reasons why this occurs.

The implications for health care are important, and that this finding could mean that drugs should be provided at a certain time of day so they can be more effective.

Or it could be designed which target drugs to the body clock to put the immune system in its most active phase.

According to Dr. Reddy, pharmaceutical companies are already studying this process and is now analyzing the supply of drugs at different times of day.

Finally, the scientist noted that "in 10 years could begin to see the impact of our biological clock in medicine."