Intestinal epithelial Toll-like receptor 4 signaling affects epithelial function and colonic microbiota and promotes a risk for transmissible colitis

Dheer, Rishu, Santaolalla, Rebeca, Davies, Julie M., Lang, Jessica K., Phillips, Matthew C., Pastorini, Cristhine, Vazquez-Pertejo, Maria T. and Abreu, Maria T. (2016) Intestinal epithelial Toll-like receptor 4 signaling affects epithelial function and colonic microbiota and promotes a risk for transmissible colitis. Infection and Immunity, 84 3: 798-810. doi:10.1128/IAI.01374-15


Author Dheer, Rishu
Santaolalla, Rebeca
Davies, Julie M.
Lang, Jessica K.
Phillips, Matthew C.
Pastorini, Cristhine
Vazquez-Pertejo, Maria T.
Abreu, Maria T.
Title Intestinal epithelial Toll-like receptor 4 signaling affects epithelial function and colonic microbiota and promotes a risk for transmissible colitis
Journal name Infection and Immunity   Check publisher's open access policy
ISSN 1098-5522
0019-9567
Publication date 2016-03-01
Year available 2016
Sub-type Article (original research)
DOI 10.1128/IAI.01374-15
Open Access Status DOI
Volume 84
Issue 3
Start page 798
End page 810
Total pages 13
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2017
Language eng
Abstract Evidence obtained from gene knockout studies supports the role of Toll-like receptor 4 (TLR4) in intestinal inflammation and microbiota recognition. Increased epithelial TLR4 expression is observed in patients with inflammatory bowel disease. However, little is known of the effect of increased TLR4 signaling on intestinal homeostasis. Here, we examined the effect of increased TLR4 signaling on epithelial function and microbiota by using transgenic villin-TLR4 mice that overexpress TLR4 in the intestinal epithelium. Our results revealed that villin-TLR4 mice are characterized by increases in the density of mucosa-associated bacteria and bacterial translocation. Furthermore, increased epithelial TLR4 signaling was associated with an impaired epithelial barrier, altered expression of antimicrobial peptide genes, and altered epithelial cell differentiation. The composition of the colonic luminal and mucosa-associated microbiota differed between villin-TLR4 and wild-type (WT) littermates. Interestingly, WT mice cohoused with villin-TLR4 mice displayed greater susceptibility to acute colitis than singly housed WT mice did. The results of this study suggest that epithelial TLR4 expression shapes the microbiota and affects the functional properties of the epithelium. The changes in the microbiota induced by increased epithelial TLR4 signaling are transmissible and exacerbate dextran sodium sulfate-induced colitis. Together, our findings imply that host innate immune signaling can modulate intestinal bacteria and ultimately the host's susceptibility to colitis.
Keyword Toll-Like Receptor 4
TLR4
Epithelial function
Colonic microbiota
Epithelial cells (ECs)
Inflammation
Colitis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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