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    Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

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    Author
    Nickerson, K. P.
    Senger, S.
    Fraser, Claire M.
    Date
    2018-05-01
    Journal
    EBioMedicine
    Publisher
    Elsevier B.V.
    Type
    Article
    
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    See at
    https://www.doi.org/10.1016/j.ebiom.2018.04.005
    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. © 2018 The Authors
    Sponsors
    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.
    Keyword
    Host-pathogen interaction
    Human tissue
    Immune evasion
    Immune system
    Innate immunity
    Intestinal organoids
    Organoid monolayer
    Salmonella
    Snapwell™ system
    Terminal ileum
    Typhoid fever
    Vaccine development
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    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046687462&origin=inward; http://hdl.handle.net/10713/9847
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ebiom.2018.04.005
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