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Abstract
While the ontogeny and recruitment of the intestinal monocyte/macrophage lineage has been studied extensively, their precise localization and function has been overlooked. Here we show by imaging the murine small and large intestines in steady-state that intestinal CX3CR1+ macrophages form an interdigitated network intimately adherent to the entire mucosal lamina propria vasculature. The macrophages form contacts with each other, which are disrupted in the absence of microbiome, monocyte recruitment (Ccr2−/−), or monocyte conversion (Nr4a1−/−). In dysbiosis, gaps exist between the perivascular macrophages correlating with increased bacterial translocation from the lamina propria into the bloodstream. The recruitment of monocytes and conversion to macrophages during intestinal injury is also dependent upon CCR2, Nr4a1 and the microbiome. These findings demonstrate a relationship between microbiome and the maturation of lamina propria perivascular macrophages into a tight anatomical barrier that might function to prevent bacterial translocation. These cells are also critical for emergency vascular repair.
Highlights
While the ontogeny and recruitment of the intestinal monocyte/macrophage lineage has been studied extensively, their precise localization and function has been overlooked
An alternative scenario could be that CCR2+ monocytes enter the intestinal lamina propria and there they convert to CX3CR1hiCCR2lo monocytes that give rise to CX3CR1+ mature macrophages
CCR2+ monocytes form a perivascular network of CX3CR1+ macrophages
Summary
While the ontogeny and recruitment of the intestinal monocyte/macrophage lineage has been studied extensively, their precise localization and function has been overlooked. The recruitment of monocytes and conversion to macrophages during intestinal injury is dependent upon CCR2, Nr4a1 and the microbiome These findings demonstrate a relationship between microbiome and the maturation of lamina propria perivascular macrophages into a tight anatomical barrier that might function to prevent bacterial translocation. The macrophages within the muscularis region closely apposed to the enteric nervous system support the neurons and contribute to both intestinal secretion and motility[13], while the macrophages in the submucosa maintain the integrity of the vasculature in this layer[14] These two populations of macrophages are at a significant distance from the lumen of the bowel, may not all be replaced from bone marrow[14,15] and as such may not perform the same functions as the very large population of mucosal lamina propria macrophages that reside adjacent to the billions of commensal bacteria with which there may be direct crosstalk[6,16]
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