Understanding resident macrophage autonomy during inflammation. (360G-Wellcome-203909_Z_16_A)

Macrophages are one of the main immune cells in the peritoneal cavity, forming the first line of defence against germs that may enter from the gut or other abdominal organs. Our lab has recently shown that in the healthy cavity peritoneal macrophages are slowly replenished by circulating cells called monocytes. In response to infection or injury in the peritoneal cavity, the majority of the resident macrophages disappear and a large influx of monocytes takes place in a process called inflammation. These monocytes give rise to inflammatory macrophages that are different from their resident macrophage counterparts. However, during the process of inflammation resolution when the abdominal cavity returns to a normal healthy state, the few remaining resident macrophages proliferate to reconstitute the normal population, while the large population of inflammatory macrophages gradually die. Our aim is to determine why monocytes recruited to the cavity during inflammation appear unable to differentiate into resident macrophages during the resolution phase of inflammation and why instead, resident cells undergo repopulation solely by proliferation in this period. By investigating these processes we will reveal how self-renewal of resident macrophages contributes to the resolution of inflammation and whether pathological consequences occur if this mechanism is impaired.