In vitro Intestinal Mucosal Epithelial Responses to Wild-Type Salmonella Typhi and Attenuated Typhoid Vaccines

Department of Pediatrics, Mucosal Biology Research Center, University of Maryland School of Medicine Baltimore, MD, USA.
Frontiers in Immunology 02/2013; 4:17. DOI: 10.3389/fimmu.2013.00017
Source: PubMed


Typhoid fever, caused by S. Typhi, is responsible for approximately 200,000 deaths per year worldwide. Little information is available regarding epithelium-bacterial interactions in S. Typhi infection. We have evaluated in vitro the effects of wild-type S. Typhi, the licensed Ty21a typhoid vaccine and the leading strains CVD 908-htrA and CVD 909 vaccine candidates on intestinal barrier function and immune response. Caco2 monolayers infected with wild-type S. Typhi exhibited alterations in the organization of tight junctions, increased paracellular permeability, and a rapid decrease in Trans-Epithelial Electrical Resistance as early as 4 h post-exposure. S. Typhi triggered the secretion of interleukin (IL)-8 and IL-6. Caco2 cells infected with the attenuated strains exhibited a milder pro-inflammatory response with minimal disruption of the barrier integrity. We conclude that wild-type S. Typhi causes marked transient alterations of the intestinal mucosa that are more pronounced than those observed with Ty21a or new generation attenuated typhoid vaccine candidates.

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Available from: Alessio Fasano, Mar 16, 2014
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    • "After evaluation of different combination of S1K3 and Salmonella in vitro, the pathogenic strain disrupted the monolayer integrity while the probiotic maintained it, even in competition with Salmonella (Fig. 2A–2F). Previous in vitro studies investigating mechanisms of Salmonella traversal have been done mostly using epithelial cell monolayers grown on permeable filters, for example, Caco-2 cells[6,28,48,60,68], and some have concluded that an alteration of epithelial tight junctions is involved. Tight junctions contain integral membrane proteins (occludin, claudins, JAM, CAR and TAMPs) and peripheral membrane proteins that directly interact with the cytoskeleton[25,36,62]. "
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