Macrophages Maintain Epithelial Barrier Integrity in the Distal Colon by Limiting the Absorption of Fluids Containing Fungal Products

Abstract

The colon is responsible for absorbing fluids. It contains many microorganisms including fungi, which are enriched in its distal segment. The colonic mucosa must thus tightly regulate fluid influx to avoid absorption of fungal metabolites, which can be toxic to epithelial cells and reach the blood circulation, leading to barrier dysfunction and sepsis. How this is achieved remains unknown. Here, we describe a mechanism by which macrophages rapidly check the fluids absorbed through epithelial cells to avoid intoxication of colonocytes. This mechanism relies on a population of distal colon macrophages equipped with balloon-like protrusions (BLPs) inserted at the base of epithelial cells. BLPs sample absorbed fluids and stop absorption when fluids contain fungal toxins. Without macrophages or BLPs, epithelial cells keep absorbing fluids containing fungal products, leading to apoptosis and loss of epithelium integrity. These results reveal an unexpected role of macrophages in the maintenance of colon-microbiota interactions in homeostasis.