| First Author | Frantz AL | Year | 2012 |
| Journal | Mucosal Immunol | Volume | 5 |
| Issue | 5 | Pages | 501-12 |
| PubMed ID | 22491177 | Mgi Jnum | J:329744 |
| Mgi Id | MGI:6840111 | Doi | 10.1038/mi.2012.23 |
| Citation | Frantz AL, et al. (2012) 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. Mucosal Immunol 5(5):501-12 |
| abstractText | 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(DeltaIEC)). 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 RegIIIgamma and Defa-rs1. We further observed significant differences in the composition of the gut microbiota between MyD88(DeltaIEC) mice and wild-type littermates. These physical, immunological, and microbial defects resulted in increased susceptibility of MyD88(DeltaIEC) mice to experimental colitis. We conclude that MyD88 signaling in IECs is crucial for maintenance of gut homeostasis. |
