Cited by 230Immune Response and InflammationGut microbiota and healthGastrointestinal motility and disorders

Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides

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Frantz, A L, Rogier, E W, Weber, C R, Shen, L, Cohen, D A, Fenton, L A, Bruno, M E C, Kaetzel, C S·2012·Mucosal Immunology

Abstract

Intestinal epithelial cells (IECs) form a physical and immunological barrier that separates the vast gut microbiota from host tissues. MyD88-dependent Toll-like receptor signaling is a key mediator of microbial-host cross-talk. We examined the role of epithelial MyD88 expression by generating mice with an IEC-targeted deletion of the Myd88 gene (MyD88(ΔIEC)). Loss of epithelial MyD88 signaling resulted in increased numbers of mucus-associated bacteria; translocation of bacteria, including the opportunistic pathogen Klebsiella pneumoniae, to mesenteric lymph nodes; reduced transmucosal electrical resistance; impaired mucus-associated antimicrobial activity; and downregulated expression of polymeric immunoglobulin receptor (the epithelial IgA transporter), mucin-2 (the major protein of intestinal mucus), and the antimicrobial peptides RegIIIγ and Defa-rs1. We further observed significant differences in the composition of the gut microbiota between MyD88(ΔIEC) mice and wild-type littermates. These physical, immunological, and microbial defects resulted in increased susceptibility of MyD88(ΔIEC) mice to experimental colitis. We conclude that MyD88 signaling in IECs is crucial for maintenance of gut homeostasis.

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  • Both TM7 and Proteobacteria are found at increased levels in the altered flora after epithelial cell-specific ablation of MyD88.

    “Both TM7 and Proteobacteria are found at increased levels in the altered flora after epithelial cell-specific ablation of MyD88 50.”

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Authors
Frantz, A. L., Rogier, E. W., Weber, C. R., Shen, L., Cohen, D. A., Fenton, L. A., Bruno, M. E. C., & Kaetzel, C. S.
Affiliations
  • University of Kentucky (US)
  • University of Chicago (US)
Corresponding author
Kaetzel, C S
Venue
Mucosal Immunology
Publisher
Elsevier BV
Published
2012-09
Volume
5
Issue
5
Pages
501-512
ISSN
1933-0219 (ISSN-L)
OpenAlex
W2015015427
Cited by
230
References
57
Citations by year
2026: 7 · 2025: 18 · 2024: 15 · 2023: 8 · 2022: 11 · 2021: 20 · 2020: 9 · 2019: 10 · 2018: 13 · 2017: 22 · 2016: 9 · 2015: 22 · 2014: 39 · 2013: 20 · 2012: 6
FWCI
12.17
Type
journal article
Language
en
Open access
Locations
  • Mucosal Immunology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Crohn's and Colitis Foundation
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R21AI069027)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
MyD88, intestinal epithelial cells, Toll-like receptor signaling, antibacterial immunity, polymeric immunoglobulin receptor, MUC2, antimicrobial peptides, RegIIIγ, Klebsiella pneumoniae, bacterial translocation, mucus-associated bacteria, gut microbiota, colitis susceptibility, intestinal barrier, intestinal homeostasis
MeSH terms
Pancreatitis-Associated Proteins, Animals, Cell Line, Colitis, Homeostasis, Humans, Intestinal Mucosa, Klebsiella Infections, Klebsiella pneumoniae, Mice, Inbred C57BL, Opportunistic Infections, Peptide Fragments, Proteins, Signal Transduction, Down-Regulation, Sequence Deletion, Mice, Knockout, Immunity, Mucosal, Receptors, Polymeric Immunoglobulin, Models, Animal, RNA, Small Interfering, Mice, Myeloid Differentiation Factor 88, Metagenome, Mucin-2

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