AUTHOR=Fiorentino Maria , Lammers Karen M., Levine Myron M., Sztein Marcelo B., Fasano Alessio 

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

JOURNAL=Frontiers in Immunology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2013.00017

DOI=10.3389/fimmu.2013.00017

ISSN=1664-3224

ABSTRACT=<p>Typhoid fever, caused by <italic>S</italic>. Typhi, is responsible for approximately 200,000 deaths per year worldwide. Little information is available regarding epithelium-bacterial interactions in <italic>S</italic>. Typhi infection. We have evaluated <italic>in vitro</italic> the effects of wild-type <italic>S</italic>. Typhi, the licensed Ty21a typhoid vaccine and the leading strains CVD 908-<italic>htrA</italic> and CVD 909 vaccine candidates on intestinal barrier function and immune response. Caco2 monolayers infected with wild-type <italic>S</italic>. 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. <italic>S</italic>. 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 <italic>S</italic>. 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.</p>