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

作者：Yanagihara Sae; Kanaya Takashi; Fukuda Shinji; Nakato Gaku; Hanazato Misaho; Wu Xue Ru; Yamamoto Naoyuki; Ohno Hiroshi^*

来源：International Immunology, 2017, 29(8): 357-363.

DOI：10.1093/intimm/dxx043

• gut immune system
• surface layer protein A
• uromodulin

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.

• 出版日期2017-8