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Updated: Apr 5, 2026
Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
Published on: May 21, 2012
Intestinal macrophages arising from CCR2(+) monocytes control pathogen infection by activating innate lymphoid cells
Sang-Uk Seo1, Peter Kuffa2, Sho Kitamoto2
1Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, 1500 E Medical Center Dr Ann Arbor, Michigan 48109, USA.
Abstract:
Monocytes play a crucial role in antimicrobial host defence, but the mechanisms by which they protect the host during intestinal infection remains poorly understood. Here we show that depletion of CCR2(+) monocytes results in impaired clearance of the intestinal pathogen Citrobacter rodentium. After infection, the de novo recruited CCR2(+) monocytes give rise to CD11c(+)CD11b(+)F4/80(+)CD103(-) intestinal macrophages (MPs) within the lamina propria. Unlike resident intestinal MPs, de novo differentiated MPs are phenotypically pro-inflammatory and produce robust amounts of IL-1β (interleukin-1β) through the non-canonical caspase-11 inflammasome. Intestinal MPs from infected mice elicit the activation of RORγt(+) group 3 innate lymphoid cells (ILC3) in an IL-1β-dependent manner. Deletion of IL-1β in blood monocytes blunts the production of IL-22 by ILC3 and increases the susceptibility to infection. Collectively, these studies highlight a critical role of de novo differentiated monocyte-derived intestinal MPs in ILC3-mediated host defence against intestinal infection.
Insights
Newly identified intestinal macrophages derived from monocytes are crucial for host defense against bacterial infections. These cells activate innate lymphoid cells, enhancing pathogen clearance and reducing infection susceptibility.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Monocytes are vital for host defense against pathogens.
- Mechanisms of monocyte-mediated protection during intestinal infections are not fully understood.
Purpose of the Study:
- To elucidate the role of monocytes in host defense against Citrobacter rodentium infection.
- To characterize the origin and function of monocyte-derived intestinal macrophages.
Main Methods:
- CCR2(+) monocyte depletion model in mice.
- Flow cytometry and cytokine analysis.
- Citrobacter rodentium infection model.
Main Results:
- Depletion of CCR2(+) monocytes impaired pathogen clearance.
- Recruited monocytes differentiated into pro-inflammatory intestinal macrophages (MPs).
- These MPs produced IL-1β via the caspase-11 inflammasome, activating ILC3s.
- IL-1β production by MPs was essential for IL-22 production by ILC3s and host defense.
Conclusions:
- De novo differentiated monocyte-derived intestinal MPs are critical for host defense.
- These MPs activate ILC3s in an IL-1β-dependent manner.
- Monocyte-derived MPs contribute to IL-22-mediated immunity against intestinal infections.
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