Abstract
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.
Highlights
Typhoid fever occurs among persons living in industrialized countries, many belonging to known risk groups, such as travelers to endemic regions, including military personnel
For some immunofluorescence staining experiments (IFL), Caco2 cells were grown on eight-well slide culture chambers (Lab Tek II, Nunc, IL, USA) and were used 2 days after confluence
Since modulation and/or disruption of epithelial barrier function can be measured by changes in Trans-Epithelial Electric Resistance (TEER), we used this technique to monitor alterations in mucosal permeability caused by the bacteria
Summary
Paratyphi A, B, and C are the causing agents of enteric fevers. Typhoid fever is an acute, life-threatening febrile illness caused by S. Typhi which results in ∼200,000 deaths worldwide each year, largely in developing nations (Crump et al, 2004). Typhoid fever occurs among persons living in industrialized countries, many belonging to known risk groups, such as travelers to endemic regions, including military personnel. Typhi and infection occurs through ingestion of contaminated food or water. In 5–10% of infected people, neuropsychiatric manifestations occur. Complications such as gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10–15% of patients (Fraser et al, 2007)
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