The role of efferocytosis in regulating inflammatory macrophage fate and response to injury in the peritoneal cavity.

Macrophages are key immune cells in peritoneal health, influencing formation of scar tissue (adhesions) that commonly occur following abdominal surgery and the outcome of bacterial infection.

What determines how peritoneal macrophages respond in these settings and whether they will promote or protect against disease remains unclear.

Resident macrophages within the cavity (RPMs) and monocyte-derived macrophages (MDMs) that infiltrate during peritoneal inflammation display different gene expression profiles and phenotypes that appear related to their difference in the level of expression of the transcription factor GATA6.

Prior research suggests these populations differ in response to bacterial infection and surgery, and that competition for uptake of dying cells may drive this difference.

I aim to understand how the level of GATA6 expression by macrophages affects infection and adhesion formation, and whether the relative proportions of these two populations alters outcome. I will study the mechanisms by which RPMs and MDMs interact with apoptotic cells and how this influences their fate.

To do so I will use a variety of genetically modified mouse lines, assessing the transcriptional profiles of RPMs and MDMs, and their effect on adhesion formation and infection clearance. This will guide a better understanding of how macrophages govern peritoneal health.