Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium.
Commensal-associated molecular patterns, the major products of nonpathogenic bacteria, are present at high concentrations at the apical surface of the intestinal epithelium. However, the nature of the interaction of commensal-associated molecular patterns with the lumenal surface of the epithelium has not been defined. We have recently demonstrated that intestinal epithelial cells constitutively express several Toll-like receptors (TLRs) in vitro and in vivo that seem to be the key receptors responsible for immune cell activation in response to various bacterial products. In this study we characterize the subcellular distribution of two major TLRs, TLR2 and TLR4, and their ligand-specific dynamic regulation in the model human intestinal epithelial cell line T84. Immunocytochemical studies indicate that TLR2 and TLR4 are constitutively expressed at the apical pole of differentiated T84 cells. After stimulation with lipopolysaccharide or peptidoglycan, TLRs selectively traffic to cytoplasmic compartments near the basolateral membrane. Thus, we demonstrate that TLRs are positioned at the apical pole where they are poised to monitor the sensitive balance of the lumenal microbial array. The results of this dynamic epithelial surveillance can then be conveyed to the underlying cell populations of the lamina propria via these innate immune pattern recognition receptors.
Cario
Elke
E
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Brown
Dennis
D
McKee
Mary
M
Lynch-Devaney
Kathryn
K
Gerken
Guido
G
Podolsky
Daniel K
DK
D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003593:Cytoplasm / Q000378:metabolism*; D029721:Drosophila Proteins; D004926:Escherichia coli; D005455:Fluorescent Antibody Technique; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013211:Staphylococcus aureus; D013347:Subcellular Fractions / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014407:Tumor Cells, Cultured
D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors