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Publication : Uromodulin-SlpA binding dictates Lactobacillus acidophilus uptake by intestinal epithelial M cells.

First Author  Yanagihara S Year  2017
Journal  Int Immunol Volume  29
Issue  8 Pages  357-363
PubMed ID  28992252 Mgi Jnum  J:248196
Mgi Id  MGI:5916924 Doi  10.1093/intimm/dxx043
Citation  Yanagihara S, et al. (2017) Uromodulin-SlpA binding dictates Lactobacillus acidophilus uptake by intestinal epithelial M cells. Int Immunol 29(8):357-363
abstractText  Bacterial access to the gut immune system is a crucial process to promote host immune responses. The probiotic L-92 strain of Lactobacillus acidophilus exerts anti-allergic immunomodulatory effects upon oral administration in mice. Here, we show that microfold cells (M cells) are responsible for L-92 internalization for evoking L-92-mediated immune responses. L-92 specifically bound to uromodulin, a glycosylphosphatidylinositol-anchored protein expressed exclusively on M cells among intestinal epithelial cells. Internalization of L-92 into M cells was significantly reduced in uromodulin-deficient (Umod-/-) mice compared to Umod+/+ mice. Furthermore, the binding of L-92 to uromodulin was significantly decreased after removal of surface layer protein A (SlpA) from the bacteria. Our study thus revealed a crucial role of uromodulin on the M-cell surface for the uptake of SlpA-positive lactic acid bacteria into M cells, possibly leading to subsequent delivery of the bacteria to dendritic cells closely associated with M cells for immunomodulation. Our study also shed light on the possibility that SlpA and uromodulin could be used as vehicle and target, respectively, for efficient mucosal vaccine delivery.
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