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.

Nature Communications
|March 14, 2020
PubMed

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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