An internal ‘clock’ that regulates the action of neutrophils, a type of leucocyte in the immune system, Spanish researchers have reported.
Dr Andres Hidalgo of the Centro Nacional de Investigaciones Cardiovasculares in Madrid, Spain, and colleagues explain that neutrophils are critical in defending against infection – but in excess can harm cells in the cardiovascular system.
The team identified a series of molecules in the nucleus and cell membrane of neutrophils that respond to circadian patterns based on the amount of lightness or darkness. These molecules regulate the movement and placement of neutrophils, as well as their removal from the circulation.
Details appeared in Immunity yesterday (29 January). Dr Hidalgo says: "The biological challenge is to control the immune system so that it protects against infection but does not cause collateral damage to the body.
"This is what happens, for example, during myocardial infarction, stroke, and acute lung injury."
To investigate further, the team used genetic techniques and high-resolution microscopy imaging on mice with myocardial infarction, stroke, or infection. This showed that the immune response changed at different times of day.
They report: "By specifically manipulating this genetic clock, we were able to make animals highly resistant to infection, but these same animals were extremely vulnerable to infarction."
When the team eliminated the clock in the neutrophils of mice, the circadian patterns in infection and infarction disappeared. They found that, during the day, the neutrophils caused more damage in an infarction, but at the same time became more efficient at eliminating pathogens.
"If we can learn to control this immune clock, we can take advantage of this association to improve treatments for patients," they state.
Adrover, J. M. A Neutrophil Timer Coordinates Immune Defense and Vascular Protection. Immunity 29 January 2019 doi: 10.1016/j.immuni.2019.01.002
https://www.cell.com/immunity/fulltext/S1074-7613(19)30002-0
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