Growing into the role: how immune cell maturity and behaviour is affected by the local population
March 2021: Members of the Jenkins lab have discovered how the maturity and behaviour of cells recruited to sites of infection or injury are influenced by the existing cell population in that area.
Having an infection or injury can affect future disease, by changing how our body’s immune system responds to new and unrelated infection and inflammation. What causes this change in immune response is not clear.
‘Resident macrophages’ are immune cells that live in our tissues for many years. They play front-line roles in defence against germs, and can also trigger inflammation. They can be thought of as live-in tissue security guards. Infection and inflammation leads to a rapid supply of these cells to the scene, recruited from the blood as precursor cells called ‘monocytes’.
In this research, we have studied the long-term effects of inflammation in the abdominal cavity of mice. We were trying to determine what controls the fate of these new cell recruits and whether they behave differently to the resident macrophages already in the abdomen.
We show that recruited macrophages become long-lived and survive in the tissue for months, and possibly years, following inflammation. However, they are kept in an immature and anti-inflammatory state because established resident macrophages are still present.
Removal of the established cells resulted in more rapid maturation of the new recruits.
As a result, inflammation leads to long-term changes in the population and function of tissue immune cells. This is because cells recruited during inflammation survive, but their development is slowed by competition with established resident macrophages.
These findings are important for understanding what predisposes some individuals to diseases of the abdominal cavity, including common conditions like endometriosis.
They also help us to understand how the long-term consequences of mild inflammation in the cavity differ from more severe inflammatory events that generally result in rapid and complete loss of established resident macrophages. Mild inflammation can be caused by events like abdominal surgery, whereas severe events can include acute infections of the peritoneal cavity, a fluid-filled space that separates our abdominal organs.
The process of competition-inhibited maturation of recruited macrophages that we describe is also likely to be broadly applicable to the chronic effects of infection and inflammation in many tissues.
Written by Steve Jenkins and Lana Woolford.