@article{8a24dd10e6c343e69645ddf9fa63068d,
title = "Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue",
abstract = "Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies.",
keywords = "Host-pathogen interaction, Human tissue, Immune evasion, Immune system, Innate immunity, Intestinal organoids, Organoid monolayer, Salmonella, Snapwell{\texttrademark} system, Terminal ileum, Typhoid fever, Vaccine development",
author = "Nickerson, {K. P.} and S. Senger and Y. Zhang and R. Lima and S. Patel and L. Ingano and Flavahan, {W. A.} and Kumar, {D. K.V.} and Fraser, {C. M.} and Faherty, {C. S.} and Sztein, {M. B.} and M. Fiorentino and A. Fasano",
note = "Funding Information: These studies were supported, in part, by NIAID, NIH, DHHS grants R01-AI036525 (to MBS), U19-AI082655 [Cooperative Center on Human Immunology] (to MBS and AF), and U19-AI109776 [Center of Excellence for Translational Research (CETR)] to MBS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases , the National Institutes of Health , NIAID, NIH. Funding Information: The EM core was supported by NIH /NINDS P30NS045776 . Support for the Philly Dake Electron Microscope Facility was provided by NIH 1S10RR023594S10 and by funds from the Dake Family Foundation. Funding Information: The authors would like to thank the Diane Capen for her expertise and skill in preparing the samples for TEM analysis. We would also like to thank members of the Fasano, Fiorentino and Faherty laboratories as well as the members of the University of Maryland Cooperative Center on Human Immunology (CCHI) for their thoughtful feedback and discussions during the development of the project. A special acknowledgment to Susie Flaherty for her careful editing of the manuscript. Funding Information: We thank Dana-Farber/Harvard Cancer Center in Boston, MA, for the use of the Specialized Histopathology Core, which provided embedding and sectioning service. Dana-Farber/Harvard Cancer Center is supported in part by an NCI Cancer Center Support Grant # NIH 5 P30 CA06516 . Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = may,
doi = "10.1016/j.ebiom.2018.04.005",
language = "English (US)",
volume = "31",
pages = "92--109",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}