The K5 capsule of Escherichia coli strain Nissle 1917 is important in stimulating expression of Toll-like receptor 5, CD14, MyD88, and TRIF together with the induction of interleukin-8 expression via the mitogen-activated protein kinase pathway in epithelial cells.
Escherichia coli strain Nissle 1917, which has been widely used as a probiotic for the treatment of inflammatory bowel disorders, expresses a K5 capsule, the expression of which is often associated with extraintestinal and urinary tract isolates of E. coli. Previously, it had been shown that the expression of a K5 capsule by Nissle 1917 was important in mediating interactions with epithelial cells and the extent of chemokine expression. In this paper, we show that infection with Nissle 1917 induces expression of Toll-like receptor 4 (TLR4) and TLR5 in Caco-2 cells and that maximal induction of TLR5 required the K5 capsule. In addition, purified K5 polysaccharide was capable of inducing expression of TLR5 and mCD14 and potentiated the activity of both TLR4 and TLR5 agonists to increase the proinflammatory response. Infection with Nissle 1917 also increased the expression of the adaptor molecules MyD88 and TRIF, which was K5 capsule dependent. By Western blot analysis, it was possible to show that induction of interleukin-8 by Nissle 1917 was predominantly through the mitogen-activated protein (MAP) kinase pathway and that expression of the K5 capsule was important for activation of the MAP kinase pathway. This paper provides new information on the function of the K5 capsule in mediating interactions between Nissle 1917 and epithelial cells and the mechanisms that underlie the probiotic properties of Nissle 1917.
Hafez
Mohamed
M
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Dover Street, Manchester M13 9PT, United Kingdom.
Hayes
Kelly
K
Goldrick
Marie
M
Grencis
Richard K
RK
Roberts
Ian S
IS
D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis; D016667:Bacterial Capsules / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D004926:Escherichia coli / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis; D015854:Up-Regulation
D033942:Adaptor Proteins, Vesicular Transport; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C470409:TICAM1 protein, human; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D020928:Mitogen-Activated Protein Kinases