| Autor: |
Nickerson, Cheryl A., Goodwin, Thomas J., Terlonge, Jacqueline, Ott, C. Mark, Buchanan, Kent L., Uicker, William C., Emami, Kamal, LeBlanc, Carly L., Ramamurthy, Rajee, Clarke, Mark S., Vanderburg, Charles R., Hammond, Timothy, Pierson, Duane L. |
| Zdroj: |
Infection and Immunity; November 2001, Vol. 69 Issue: 11 p7106-7120, 15p |
| Abstrakt: |
ABSTRACTThe lack of readily available experimental systems has limited knowledge pertaining to the development ofSalmonella-induced gastroenteritis and diarrheal disease in humans. We used a novel low-shear stress cell culture system developed at the National Aeronautics and Space Administration in conjunction with cultivation of three-dimensional (3-D) aggregates of human intestinal tissue to study the infectivity of Salmonella entericaserovar Typhimurium for human intestinal epithelium. Immunohistochemical characterization and microscopic analysis of 3-D aggregates of the human intestinal epithelial cell line Int-407 revealed that the 3-D cells more accurately modeled human in vivo differentiated tissues than did conventional monolayer cultures of the same cells. Results from infectivity studies showed thatSalmonellaestablished infection of the 3-D cells in a much different manner than that observed for monolayers. Following the same time course of infection with Salmonella, 3-D Int-407 cells displayed minimal loss of structural integrity compared to that of Int-407 monolayers. Furthermore, Salmonellaexhibited significantly lower abilities to adhere to, invade, and induce apoptosis of 3-D Int-407 cells than it did for infected Int-407 monolayers. Analysis of cytokine expression profiles of 3-D Int-407 cells and monolayers following infection with Salmonellarevealed significant differences in expression of interleukin 1α (IL-1α), IL-1β, IL-6, IL-1Ra, and tumor necrosis factor alpha mRNAs between the two cultures. In addition, uninfected 3-D Int-407 cells constitutively expressed higher levels of transforming growth factor β1 mRNA and prostaglandin E2than did uninfected Int-407 monolayers. By more accurately modeling many aspects of human in vivo tissues, the 3-D intestinal cell model generated in this study offers a novel approach for studying microbial infectivity from the perspective of the host-pathogen interaction. |
| Databáze: |
Supplemental Index |
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