Regulation of the polymeric immunoglobulin receptor in intestinal epithelial cells by Enterobacteriaceae: implications for mucosal homeostasis.
The commensal microbiota of the human colon profoundly impacts host gene expression and mucosal homeostasis. Secretory IgA antibodies, which influence the composition of the intestinal microbiota and provide immunity against pathogens, are transported across intestinal epithelial cells (IEC) by the polymeric immunoglobulin receptor (pIgR). To compare the effects of different colonic bacteria on pIgR expression, the human IEC line HT-29 was stimulated with various species representing the 4 major phyla of colonic bacteria. Only bacteria from the family Enterobacteriaceae (phylum Proteobacteria) induced expression of pIgR and other target genes of bacterial pattern recognition receptors. HT-29 cells responded to purified ligands for Toll-like receptor (TLR)4 but not TLR2. Expression of pIgR and transport of IgA were significantly reduced in colons of mice deficient in the TLR adaptor MyD88, consistent with a role for TLR signaling in the regulation of pIgR by colonic bacteria. Induction of pIgR expression in HT-29 cells required NF-kappaB signaling but not MAPK signaling, in contrast to the requirement for both NF-kappaB and MAPK signaling for induction of pro-inflammatory genes. These results suggest that commensal Enterobacteriaceae may promote intestinal homeostasis by enhancing pIgR expression in IEC.
Bruno
Maria E C
ME
Department of Microbiology, Immunology & Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536, USA.
Rogier
Eric W
EW
Frantz
Aubrey L
AL
Stefka
Andrew T
AT
Thompson
Stephanie N
SN
Kaetzel
Charlotte S
CS
D000818:Animals; D004755:Enterobacteriaceae / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D019073:HT29 Cells; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D019056:Receptors, Polymeric Immunoglobulin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology
D007070:Immunoglobulin A; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin