Educating scavenger immune cells: why sex is important
June 2020: Researchers from the Bain and Jenkins labs discover that immune cells called macrophages get a better education in the female abdomen, making them more effective scavengers of harmful bacteria.
The body’s immune system is there to protect against attack from infection. Macrophages are cells of the immune system that are present in every tissue/organ of the body and are specialised at scavenging and killing bacteria. Macrophages develop from immature precursor cells called monocytes that circulate in the bloodstream.
As macrophages develop from monocytes, they are ‘educated’ to perform their crucial scavenger functions by the local tissue environment. However, until now this ‘education’ was thought to occur rapidly, with monocytes quickly adapting once they arrive from the blood.
In our present study, we have used mice to understand macrophage education in the abdominal or 'peritoneal' cavity and show that this process differs markedly between males and females. Critically, we found that some functions of macrophages took a long time to develop within the tissue.
In females, peritoneal macrophages live for a very long time, thereby allowing a thorough and prolonged education process to occur. Part of this involves changes to the machinery present on the cell surface to detect bacteria, including a bacterial receptor called CD209b. As a result, female macrophages in the cavity are better equipped to detect, engulf and kill bacterial intruders. In contrast, peritoneal macrophages in male mice are more rapidly replaced by their monocyte precursor cells, meaning their education is cut short.
The research shows that prolonged education of female macrophages is dependent on local signals from the ovaries and that surgical removal of the ovaries (oophorectomy) renders female macrophages more short-lived like their male counterparts. The Bain and Jenkins groups propose that the superior bacterial handling ability of female peritoneal macrophages has evolved as a protection mechanism for the female reproductive tract. This is particularly important given the anatomical differences in the peritoneal cavity between the sexes.
Unlike in males where the peritoneal cavity is entirely enclosed, the lining of the peritoneal cavity (called the peritoneum) is open around the fallopian tubes, meaning there is potential for retrograde passage of bacteria from within the reproductive tract into the cavity. Ensuring this is eliminated quickly and efficiently is vital to prevent inflammation of the peritoneum, termed peritonitis.
Peritoneal macrophages have also been implicated in diseases such as endometriosis, a condition where tissue similar to that found in the uterus starts to grow outside the uterus, including in the peritoneal cavity. Thus, understanding how macrophage education changes in the context of chronic disease could lead to the development of new therapies for these conditions. An important first step in this process will be to determine if our findings in mice are also present in humans.