Abstract
The colon is primarily responsible for absorbing fluids. It contains a large number of microorganisms including fungi, which are enriched in its distal segment. The colonic mucosa must therefore tightly regulate fluid influx to control absorption of fungal metabolites, which can be toxic to epithelial cells and lead to barrier dysfunction. How this is achieved remains unknown. Here, we describe a mechanism by which the innate immune system allows rapid quality-check of absorbed fluids to avoid intoxication of colonocytes. This mechanism relies on a population of distal colon macrophages that are equipped with "balloon-like" protrusions (BLPs) inserted in the epithelium, which sample absorbed fluids. In the absence of macrophages or BLPs, epithelial cells keep absorbing fluids containing fungal products, leading to their death and subsequent loss of epithelial barrier integrity. These results reveal an unexpected and essential role of macrophages in the maintenance of colon-microbiota interactions in homeostasis.
Highlights
The gut is a unique environment that is continuously exposed to food antigens and to a rich community of micro-organisms
This is true for macrophages (Mφs), which are present in greater numbers in the colon compared to the small intestine
We found that hydrazide was more abundant in the blood of Mφ-depleted mice compared to control animals (Figure 1D, [20]), indicating a loss of barrier integrity in these animals. These results show that Mφ are required for epithelial cell survival and intestinal barrier integrity in the distal colon
Summary
The gut is a unique environment that is continuously exposed to food antigens and to a rich community of micro-organisms. Fungi, which are abundant in the distal colon [7], can produce metabolites that trigger apoptosis of intestinal epithelial cells [8], thereby potentially compromising the integrity of the intestinal barrier. In the absence of macrophages or BLPs, epithelial cells continue to take up fluids containing fungal products, resulting in their death and subsequent loss of epithelial barrier integrity These results [20] revealed for the first time an unexpected and essential role for macrophages in maintaining interactions between the colonic epithelial barrier and the microbiota, playing a key role in the maintenance of intestinal homeostasis
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