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Updated: Sep 17, 2025
Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Fibroblast-derived CSF1 maintains colonization of gut mucosal macrophage to resist bacterial infection
Daichi Nonaka1, Soichiro Yoshida1, Kenta Nakano2
1Division of Mucosal Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Abstract:
Macrophages play essential roles in immune defense and tissue homeostasis, but the mechanisms underlying their colonization in the gut mucosa remain incompletely understood. Here, we identify CSF1, primarily derived from fibroblasts, as the dominant factor maintaining mucosal macrophage colonization, whereas IL-34 deficiency alone has a minimal impact. We reveal that CSF1R ligands originate from distinct cellular sources: macrophages at the upper villus region depend on fibroblast-derived CSF1 and IL-34, while macrophages in the lower villus and the submucosal (lower villus + SM) region are regulated by CSF1 from both fibroblasts and endothelial cells. Additionally, within the lower villus + SM region, CSF1-producing CD81+ LepR+ fibroblasts directly interact with CD163+ macrophages, forming a localized niche. The loss of CSF1 in fibroblasts results in accelerated systemic dissemination of Salmonella Typhimurium, highlighting fibroblast-derived CSF1 as a key regulator of gut macrophage function in host defense. Collectively, our findings uncover a previously unrecognized fibroblast-macrophage crosstalk that governs gut macrophage homeostasis and immunity.
Insights
Fibroblast-derived CSF1 is crucial for maintaining gut macrophage populations and host defense. Its absence accelerates Salmonella Typhimurium spread, revealing a key fibroblast-macrophage communication pathway in the gut.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Macrophages are vital for gut immunity and tissue balance.
- Mechanisms of gut mucosal macrophage colonization are not fully understood.
Purpose of the Study:
- To identify key factors regulating macrophage colonization in the gut mucosa.
- To elucidate the cellular origins and interactions governing gut macrophage homeostasis.
Main Methods:
- Investigated the roles of CSF1 and IL-34 in macrophage colonization.
- Analyzed ligand sources from fibroblasts, endothelial cells, and macrophages.
- Examined fibroblast-macrophage interactions in specific gut regions.
- Assessed the impact of CSF1 deficiency on Salmonella Typhimurium infection.
Main Results:
- Fibroblast-derived CSF1 is the primary factor for mucosal macrophage colonization, more so than IL-34.
- Macrophage regulation varies by gut region, with distinct ligand sources (fibroblasts, endothelial cells).
- Specific fibroblast (CD81+ LepR+) and macrophage (CD163+) interactions form a niche in the lower gut.
- Loss of fibroblast CSF1 leads to increased Salmonella Typhimurium dissemination.
Conclusions:
- Fibroblast-derived CSF1 is essential for gut macrophage homeostasis and host defense.
- A novel fibroblast-macrophage crosstalk pathway regulates gut immunity.
- Targeting this pathway could impact gut health and infectious disease outcomes.
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