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Updated: Dec 26, 2025

Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
Published on: May 21, 2012
Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome
Masaki Honda1,2, Bas G J Surewaard1, Mayuki Watanabe1
1Department of Physiology and Pharmacology, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
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.
Insights
Intestinal macrophages form a vascular network that prevents bacterial translocation. Microbiome and specific genes are crucial for their function and repair capabilities.
Area of Science:
- Immunology
- Gastroenterology
- Microbiology
Background:
- The development and role of intestinal macrophages are not fully understood.
- Their precise location and function within the gut lining remain unclear.
Purpose of the Study:
- To investigate the localization and function of intestinal macrophages in the gut lamina propria.
- To determine the role of the microbiome and specific genetic factors in macrophage network integrity and function.
Main Methods:
- In vivo imaging of murine small and large intestines.
- Analysis of gene-deficient models (Ccr2-/- and Nr4a1-/-).
- Assessment of bacterial translocation under different conditions (steady-state, dysbiosis).
Main Results:
- Intestinal CX3CR1+ macrophages form an interconnected network along the mucosal vasculature.
- This network's integrity depends on the microbiome, Ccr2, and Nr4a1.
- Disruption of this network correlates with increased bacterial translocation during dysbiosis.
- Monocyte recruitment and conversion are dependent on CCR2, Nr4a1, and the microbiome.
Conclusions:
- The gut microbiome influences the maturation of perivascular macrophages into a barrier preventing bacterial translocation.
- These macrophages are essential for maintaining gut barrier integrity and vascular repair.
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