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A role for stem cell factor (SCF): c-kit interaction(s) in the intestinal tract response to Salmonella typhimurium
G R Klimpel1, K E Langley, J Wypych
1Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, 77555-1019, USA.
Abstract:
Cholera toxin (CT) has been shown to induce stem cell factor (SCF) production in mouse ligated intestinal loops. Further, SCF interaction(s) with its receptor (c-kit) was shown to be important for the intestinal tract secretory response after CT exposure. In this study, we have investigated whether SCF production is induced in the intestinal tract after exposure to Salmonella typhimurium and whether this production could be an important intestinal tract response to Salmonella infection. Using a mouse ligated intestinal loop model, increased levels of SCF mRNA were detected at 2-4 h post-Salmonella challenge. Intestinal fluid obtained from Salmonella-challenged loops contained high levels of SCF by ELISA. Human and murine intestinal epithelial cell lines were also shown to have increased levels of SCF mRNA after exposure to Salmonella. Inhibition of Salmonella invasion of epithelial cells was shown to be one potentially important role for SCF:c-kit interactions in host defense to Salmonella infection. Pretreatment of human or murine intestinal cell lines with SCF resulted in a cellular state that was resistant to Salmonella invasion. Finally, mice having mutations in the white spotting (W) locus, which encodes the SCF-receptor (c-kit), were significantly more susceptible to oral Salmonella challenge than their control littermates. Taken together, the above results suggest that an important intestinal tract response to Salmonella infection is an enhanced production of SCF and its subsequent interactions with c-kit.
Insights
Salmonella infection triggers stem cell factor (SCF) production in the intestine, which helps epithelial cells resist bacterial invasion. This SCF-c-kit pathway is crucial for host defense against Salmonella.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Cholera toxin (CT) induces stem cell factor (SCF) production, crucial for intestinal secretory response via c-kit.
- The role of SCF in Salmonella typhimurium infection remains largely unexplored.
Purpose of the Study:
- To investigate SCF induction in the intestinal tract following Salmonella exposure.
- To determine the role of SCF-c-kit interactions in host defense against Salmonella infection.
Main Methods:
- Utilized a mouse ligated intestinal loop model to assess SCF mRNA and protein levels post-Salmonella challenge.
- Employed human and murine intestinal epithelial cell lines to evaluate Salmonella invasion and SCF treatment effects.
- Examined Salmonella susceptibility in mice with mutations in the c-kit receptor (W locus).
Main Results:
- Salmonella challenge significantly increased SCF mRNA and protein levels in mouse intestinal loops.
- Salmonella exposure elevated SCF mRNA in human and murine intestinal epithelial cells.
- SCF pretreatment rendered intestinal cells resistant to Salmonella invasion, and W locus mutant mice showed increased susceptibility.
Conclusions:
- Salmonella infection induces intestinal SCF production, a key component of the host defense mechanism.
- SCF-c-kit signaling plays a critical role in protecting the intestinal tract against Salmonella invasion.
- Enhanced SCF production represents an important intestinal response to Salmonella infection.