Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling

Camille Jung., et al. J Clin Invest. 2012; 122(6):2239–2251.

Speaker: Chun-Yi Lai (賴君宜)                            Time: 14:00~15:00, Jan. 2, 2013

Commentator: Dr. Lien-I Hor (何漣漪博士)       Place: Room 601

Abstract:

The intestinal mucosa forms a barrier that limits the entrance of the luminal pathogens. Epithelial cells that line mucosal surfaces are an important mechanical barrier that separates the host’s internal milieu from the external environment and prevents microbes from entering epithelial cells.Paracellular permeability and transcellular transport are the two ways to allow small molecules passing from the lumen to the internal milieu. The paracellular permeability is determined by the pore of tight junctions (TJ). Large particles and microbes transported by transcellular transport need M cells overlying Peyer’s patches (PPs). Yersinia pseudotuberculosis is a species of gram-negative bacterium belonging to the family Enterobacteriaceae. Y. pseudotuberculosis is an enteropathogenic bacterium which invades the intestinal barrier by a mechanism dependent on M cells. The bacteria enter into PPs and induce mucosal inflammation. TLR-2 plays a crucial role in initiating and regulating the host response to Y. pseudotuberculosis. There are many kinds of cells in the PPs. The specific aim in this study is to understand after Y. pseudotuberculosis invades the PPswhich cell expresses TLR-2 to disrupt the intestinal barrier integrity. The authors used PPs in transwell chambers and exposed to Y. pseudotuberculosis. Then FD4 is added and the fluorescence in the lower compartment is measured. The authors also used mice to inoculate intragastrically (i.g.) with Y. pseudotuberculosis, feed FD4 and measure fluorescence in serum. The data shows that Y. pseudotuberculosis uses a virulence plasmid encoding a type III secretion system to induce TLR-2 expression of hematopoietic cells. Hematopoietic cells activate capase-1 and produce IL-1β. The author uses not only in vivo study but also in vitro study to understand the relationship between IL-1β production and intestinal barrier integrity disruption. The data shows that IL-1β stimulates NF-κB activation and increases MLCK protein expression in intestinal epithelial cells. MLCK increases TJ width and redistribution of occludin. Finally, Y. pseudotuberculosis disrupts intestinal barrier integrity.

References:

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2.          Al-Sadi R., et al.Mechanism of IL-1β-induced increase in intestinal epithelial tight junction permeability. J Immunol. 2008; 180(8):5653–5661.