Lactobacillus delbrueckii ssp. lactis R4 prevents Salmonella typhimurium SL1344-induced damage to tight junctions and ad
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I 10.1007/s12275-012-1596-5
Lactobacillus delbrueckii ssp. lactis R4 Prevents Salmonella typhimurium SL1344-Induced Damage to Tight Junctions and Adherens Junctions Qinghua Yu, Liqi Zhu, Zhisheng Wang, Pengcheng Li, and Qian Yang* Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, P. R. China (Received December 8, 2011 / Accepted April 25, 2012)
Cell junctions are the gatekeepers of the paracellular route and defend the mucosal barrier. Several enteropathogenic bacteria can invade intestinal epithelial cells by targeting and damaging cell junctions. It is not well understood how Salmonella typhimurium is able to overcome the intestinal barrier and gain access to the circulation, nor is it understood how Lactobacillus prevents the invasion of S. typhimurium. Therefore, we sought to determine whether infection with S. typhimurium SL1344 could regulate the molecular composition of cell junctions and whether Lactobacillus delbrueckii ssp. lactis R4 could affect this modification. Our data demonstrated that infection of Caco-2 cells with S. typhimurium over 2 h resulted in a redistribution of claudin-1, ZO-1, occluding, and E-cadherin. Western blot analysis of epithelial cell lysates demonstrated that S. typhimurium could decrease the expression of cell junction proteins. However, L. delbrueckii ssp. lactis R4 ameliorated this destruction and induced increased expression of ZO-1, occludin, and E-cadherin relative to the levels in the control group. The results of these experiments implied that S. typhimurium may facilitate its uptake and distribution within the host by regulating the molecular composition of cell junctions. Furthermore, Lactobacillus may prevent the adhesion and invasion of pathogenic bacteria by maintaining cell junctions and the mucosal barrier. Keywords: Lactobacillus, S. typhimurium, tight junction, adherens junction Introduction The intestinal mucosal barrier, which is composed of mucosal epithelium, a slime layer, the mucosal immune system and the normal micropopulation, plays an important role in defending against the invasion and diffusion of enteropathogenic microorganisms (Deitch, 2002). The cell junctions encircling gastrointestinal epithelial cells are also a critical component of the mucosal barrier. Tight junctions and ad*For correspondence. E-mail: [email protected]; Tel.: +86-025-84395817; Fax: +86-025-84398669
herens junctions are located between the lateral membranes of epithelial cells. The intracellular space between epithelial cells forms the paracellular route between adjacent cells, and the tight junctions and adherens junctions control the diffusion of fluid, electrolytes, macromolecules and pathogens along the paracellular route (Gumbiner, 1993). Tight junctions are composed of several proteins including transmembrane proteins (occludin and the claudins) and intracellular proteins (ZOs) (Furuse et al., 1993). E-cadherin is a transmembrane protein that is part of the adherens junction and controls the correct assembly of tight junctions. However, it has become
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