Language
English
Publication Date
1-23-2026
Journal
Science Immunology
DOI
10.1126/sciimmunol.adr4057
PMID
41544147
PMCID
PMC13016028
PubMedCentral® Posted Date
3-26-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Intestinal macrophages are essential for epithelial barrier repair. In homeostasis, macrophages are continuously replenished by recruitment of circulating CCR2+ monocytes into the intestinal lamina propria. This requires the commensal microbiota, however, the specific microbial factors and downstream host pathways that coordinate macrophage replenishment are inadequately understood. Here, we show that colonization with an E. coli isolate increased CCR2+ macrophages in the intestine and ameliorated pathology in a colitis model. Using human colonic organoids, we showed E. coli colonization induced CCL2 secretion by intestinal epithelial stem cells which promoted monocyte migration. In vivo, protection was abolished in the absence of epithelial CCL2. By screening a panel of E. coli, we identified high flagellin expression correlated with epithelial CCL2 production. Demonstrating a requirement for E. coli flagellin, in vivo protection was lost in mice lacking epithelial TLR5 or after colonization with flagellin-deficient E. coli. Collectively, our study reveals that epithelial TLR5–flagellin sensing recruits CCR2+ macrophages to the intestine, promoting barrier repair.
Keywords
Toll-Like Receptor 5, Animals, Macrophages, Humans, Mice, Intestinal Mucosa, Flagellin, Escherichia coli, Signal Transduction, Chemokine CCL2, Receptors, CCR2, Intestinal Barrier Function, Mice, Knockout, Mice, Inbred C57BL, Colitis
Published Open-Access
yes
Recommended Citation
Tsai, Ming-Ting; Callaghan, Ryann; Ng, Charles; et al., "Intestinal Epithelial TLR5 Signaling Promotes Barrier-Supportive Macrophages" (2026). Faculty, Staff and Students Publications. 6976.
https://digitalcommons.library.tmc.edu/baylor_docs/6976